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The prevalence of early repolarization in otherwise normal electrocardiograms as a function of age was evaluated in 2335 Veteran male patients. Thirty-one percent of the patients <35years of age had early repolarization, whereas only 5% of patients >65years of age demonstrated this phenomenon. In addition, only 12% of female patients <35years of age had early repolarization., (Published by Elsevier Inc.)

Serial comparison of electrocardiograms (ECGs) is a useful tool in clinical diagnostic ECG and an enhancement to computer ECG analysis. When an analysis algorithm is modified, the corresponding serial comparison program needs to be updated accordingly. The new Philips diagnostic algorithm increased the number of leads in the ECG from the traditional 12 leads to 16, making it possible to diagnose right ventricular infarct/injury based on right-sided lead V4R. To keep pace with the widespread reperfusion therapy for acute myocardial infarct, the serial comparison program was revised to recognize the rapid ECG changes in patients with ST-elevation myocardial infarct following successful reperfusion therapies. The serial comparison program was also enhanced to split "combined" statements in the category of ventricular conduction delay (includes incomplete ventricular conduction delay and bundle-branch blocks) and compare each of the statements separately., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A comparison was performed between the points measured using the Selvester QRS scoring system in 60 electrocardiograms (ECGs) displayed in both a standard format as well as a 4-fold magnified (quad-plot) format. Fifty criteria (a maximum possibility of 31 points) were evaluated in each ECG. The data indicate that in 50% of the ECGs, an identical number of points were measured. However, there was a single point difference in 31%, 2 points in 15%, and more than 2 points in 4%. The differences were primarily because of points scored on the quad-plot but not on the standard ECG. Thus, a systematic underestimation of infarct size may occur when the Selvester QRS score is measured manually from a standard ECG.

Serial comparison of electrocardiograms (ECGs) can provide a useful clinical function by reporting to the editing cardiologist the diagnostic changes that have occurred since the previous ECG. This program detects "significant measurement differences" in each of the diagnostic categories to detect these changes. We evaluated the accuracy and use of this serial comparison program by comparing the diagnostic results of the program with those of an expert cardiologist using a database of ECGs obtained from patients with symptoms admitted to the hospital and other laboratory results consistent with acute myocardial infarction. We found that the level of agreement between the computer and the cardiologist was much higher when a current ECG was compared with a previous that had been edited by the cardiologist than when that same ECG was analyzed in isolation.

Although the Selvester Scoring System for estimating the size of myocardial infarction from the standard 12-lead electrocardiogram (ECG) has potential clinical value, it has found limited application because of the difficulties in making precise and reproducible measurements. The objective of this study was to develop software to automate the Selvester Scoring System, thus allowing wider application of the technique. The study was carried out using a training set consisting of ECG data recorded from 705 individuals with and without previous myocardial infarction. Algorithms for the 50 criteria in the Selvester Scoring System were iteratively improved by comparison of scores obtained by 2 experienced cardiologist investigators with those generated by the program. The final version was evaluated in a test set consisting of 60 ECGs by comparing scores derived by cardiologist investigator with those obtained by the program. The disagreements occurred only in 1.1% of the score comparisons and in 1.6% of the specific measurements. In all cases in which a disagreement occurred, it resulted from very small differences in measurements. These results indicate that the algorithm for automated application of the Selvester Scoring System is adequate for both clinical and research applications.

Study Objectives: To determine the utility of the ECG for predicting clinical status in adults with primary pulmonary hypertension (PPH) or pulmonary arterial hypertension (PAH) secondary to collagen vascular disease., Design: Retrospective study., Setting: Outpatient clinic in a tertiary referral center., Patients: Adult outpatients with PPH or PAH secondary to collagen vascular disease who underwent electrocardiography within 30 days of undergoing right-heart catheterization, echocardiography, and 6-min walk testing., Interventions: None., Measurements and Results: The following measurements were recorded from each ECG: P-wave amplitude in lead II; mean frontal QRS axis; QRS duration; R-wave and S-wave deflections in leads I and V6; and the T-wave configurations in the precordial leads. These ECG variables were correlated with hemodynamic variables, RV size, and exercise capacity. Of the 61 patients included in this study, 56 (92%) were women. Eight of 61 patients (13%) had normal findings on ECGs. There was no significant difference in the demographics or hemodynamics when comparing groups with normal vs abnormal ECGs. All ECG parameters had no more than moderate correlation with hemodynamic variables, ventricular size measured by echocardiogram, and exercise capacity as measured by a 6-min walk. The best correlation was between mean the frontal QRS axis and cardiac index (r = -0.46)., Conclusions: The ECG is an inadequate screening tool to rule out the presence of clinically relevant pulmonary hypertension, either primary or secondary to collagen vascular disease. The mean frontal QRS axis correlated best with the severity of hemodynamic impairment.

Severe left ventricular volume overloading causes myocardial and cellular contractile dysfunction. Whether this is also true for severe right ventricular volume overloading was unknown. We therefore created severe tricuspid regurgitation percutaneously in seven dogs and then observed them for 3.5-4.0 yr. All five surviving operated dogs had severe tricuspid regurgitation and right heart failure, including massive ascites, but they did not have left heart failure. Right ventricular cardiocytes were isolated from these and from normal dogs, and sarcomere mechanics were assessed via laser diffraction. Right ventricular cardiocytes from the tricuspid regurgitation dogs were 20% longer than control cells, but neither the extent (0.171 +/- 0.005 microm) nor the velocity (2.92 +/- 0.12 microm/s) of sarcomere shortening differed from controls (0.179 +/- 0.005 microm and 3.09 +/- 0.11 microm/s, respectively). Thus, despite massive tricuspid regurgitation causing overt right heart failure, intrinsic right ventricular contractile function was normal. This finding for the severely volume-overloaded right ventricle stands in distinct contrast to our finding for the left ventricle severely volume overloaded by mitral regurgitation, wherein intrinsic contractile function is depressed.

The primary cause of restenosis following directional coronary atherectomy (DCA) remains obscure. "Negative remodeling," a decrease in vessel area, is believed to be more causative than is increase in plaque area. The DCA technique used in these patients, designed to facilitate the removal of plaque, should allow a more precise evaluation of the relative roles of these two mechanisms. Twenty-five patients underwent DCA. In 17, complete angiographic and intravascular ultrasound (IVUS) images were obtained before and after DCA and at follow-up (6 to 9 months). Internal elastic lamina (IEL), lumen, and plaque areas were calculated at preatherectomy, postatherectomy, and follow-up. Postatherectomy, the mean IEL area increased by 32% and the mean plaque area decreased by 51%, resulting in a significant mean increase in lumen area, 500%. At follow-up when compared to postatherectomy, the change in IEL area was variable; however, the mean did not change significantly (p = 0.58). Plaque area change, when standardized for initial vessel size, was small (mean increase 2.8 +/- 3.5%). The mean lumen area did not decrease significantly at follow-up (p = 0.43). A highly significant correlation (r = 0.96) was noted between IEL area change and lumen area at follow-up. In contrast, the correlation between plaque area change and lumen area change over the same period was much less significant (r = 0.64). These data indicate that decrease in IEL area primarily is responsible for restenosis.

We describe a patient with African tick-bite fever who acquired his infection while visiting rural areas of South Africa and then became sick after returning to the United States. The dominant clinical feature of his illness was the presence of multiple, ulcerated lesions (tache noires). Physicians in the United States and other non-African countries who see travelers returning from southern parts of Africa who give a history of recent tick bite and/or present with multiple, crusted or vesicular skin lesions should be alert to this diagnosis and institute treatment with doxycycline.

In canine right atrial hypertrophy, the cross-sectional area (Axs) of right atrial myocytes increases, whereas the Axs of the broader interatrial band myocytes does not. In the current study, myocyte reconstructions showed that right atrial myocyte length increased in proportion to Axs in right atrial hypertrophy. On the other hand, mean interatrial band myocyte length in both normal and right atrial hypertrophy dogs was roughly inversely proportional to mean Axs, as expected if interatrial band myocyte volume was constant. Plotting mean Axs vs. myocyte length for individual interatrial band myocytes revealed a distribution whose border defined a maximal volume curve; many myocytes were well beneath that curve. Mononuclear myocytes (generally diploid) were limited by a 65,000-micrometer 3 curve, which many binuclear myocytes (generally tetraploid) surpassed; myocyte ploidy thus constrained myocyte volume. However, because many mononuclear and binuclear myocytes had lower volumes, their failure to hypertrophy cannot be attributed to attainment of the maximal volume possible for their ploidy.

The primary purpose of this study was to define regional blood flow in dogs with chronic tricuspid regurgitation (TR) in order to determine if the marked hypertrophy of the right atria resulted in compromised myocardial perfusion. Myocardial blood flow (ml/min/gm) was measured with radiolabeled microspheres in eight dogs with TR during rest, moderate exercise (5 dogs), and infusion of adenosine (1 mg/kg/min), an index of minimal vascular resistance. Similar measurements were obtained in eight normal dogs. In TR, the ratio of right atrium (RA) and right ventricle (RV) to body weight was greater than in normal dogs, 77% and 30%, respectively. During rest, flow in the RA appendage was less than in nonappendage region in the normal dogs; no differences were noted in TR dogs, indicating an augmented hemodynamic role of the appendage in TR. Both RA and RV blood flow was greater in TR during rest but no other differences in flow were found between the two groups. Minimum vascular resistance in RV but not RA was slightly increased in TR versus normal. During marked myocyte hypertrophy, the vasculature of RA develops sufficiently to provide the same flow capacity as in the normal heart.

Vascular reserve, which defines the capacity for further vasodilation in a given physiological or pathological condition, has not been measured in the canine atria. This study defines, in normal dogs, the regional vascular reserve simultaneously measured in the atria (appendage, nonappendage regions) and in the ventricles during rest and two levels of exercise. Blood flow was determined using 11.4 +/- 0.1 microns radiolabeled microspheres. Vascular reserve (percent for each region) is the ratio of vascular conductance during each condition to maximum vascular conductance. Maximum vascular conductance was estimated by infusing adenosine intravenously. For a given physiological condition regional vascular conductance varied two- to threefold. The vascular reserve of each of the regions decreased progressively from rest to mild exercise to moderate exercise. Regional vascular reserve for both atria, the right ventricle, and the epicardial layer of the left ventricle was essentially uniform for a given condition: rest 93 +/- 0.4%, mild exercise 81 +/- 1.2%, and moderate exercise 69 +/- 1.5%. This similarity in vascular reserve implies that for a given physiological condition a common mechanism precisely regulates myocardial perfusion in these cardiac regions as a function of the total vasodilator capacity.

To investigate regional variation of myocyte response to atrial hypertrophy, control dogs were compared with dogs with right atrial hypertrophy created by induction of tricuspid regurgitation; after 1 yr, right atrial-to-body weight ratio increased 122% over controls. One section from the interatrial band, appendage and nonappendage roofs, and nonappendage side of each atrium of each dog was stained to reveal myocyte outlines and transverse tubules; myocyte cross-sectional areas were measured and transverse tubule prevalence was estimated. In control dogs, interatrial band myocytes were significantly larger and had more transverse tubules than other atrial myocytes. With atrial hypertrophy, right interatrial band myocytes did not increase significantly in size, whereas other right atrial myocytes nearly doubled in size, approaching the size of interatrial band myocytes without approaching the content of transverse tubules. Left atrial myocytes did not increase in size. Thus hypertrophic response of atrial myocytes to hemodynamic stress depends on the region in which the myocytes are found, and atrial hypertrophy does not demand transverse tubule proliferation.

Regional myocardial oxygenation was assessed during partial and complete coronary artery occlusion using near infrared spectroscopy. In eight open-chest dogs, partial occlusions resulting in an approximately 42% decrease in left anterior descending coronary artery (LAD) blood flow produced an approximately 21% decrease in tissue O2 stores (tissue oxyhemoglobin plus oxymyoglobin) and no change in the oxidation level of mitochondrial cytochrome aa3. An approximately 81% reduction in LAD blood flow produced nadir levels of tissue oxyhemoglobin plus oxymyoglobin, maximal levels of deoxyhemoglobin plus deoxymyoglobin, a decline in tissue blood volume, and an approximately 39% decrease in cytochrome aa3 oxidation level. These changes were associated with an approximately 52% decrease from the preischemic baseline in mean transmural myocardial blood flow, measured by radiolabeled microspheres, and an approximately 41% decrease in myocardial O2 consumption. Complete occlusion resulted in further decreases in myocardial blood flow, O2 consumption, tissue blood volume, and cytochrome aa3 oxidation state but also produced increases in tissue O2 stores to above the nadir levels noted during partial occlusion. These results indicate that decreases in O2 delivery during partial coronary occlusion increase O2 extraction to sustain mitochondrial O2 availability, but as little as a 52% reduction in myocardial blood flow produces maximal O2 extraction and depletion of tissue O2 stores. Mitochondrial O2 availability is restricted further during complete occlusion because of limited O2 delivery and, possibly, decreases in tissue blood volume and O2 extraction.

Global and regional atrial blood flow was measured with radioisotope-labeled microspheres in eight dogs during rest and two levels of exercise. Both mean right and left atrial blood flow increased significantly (P < 0.05) to a similar degree with each level of exercise (right atria: 0.27 +/- 0.04, 0.89 +/- 0.11, and 1.57 +/- 0.21 ml.min-1 x g-1; left atria: 0.35 +/- 0.04, 0.90 +/- 0.09, and 1.61 +/- 0.17 ml.min-1 x g-1). Atrial blood flow during exercise is greater than anticipated if increased heart rate was the sole cause. In both right and left atria the ratio of appendage to nonappendage flow was significantly (P < 0.005) less than one during resting conditions (0.42 +/- 0.04 and 0.81 +/- 0.05, respectively), not different from unity during mild exercise, and significantly (P < 0.02) greater than one during moderate exercise (1.10 +/- 0.03 and 1.16 +/- 0.05, respectively). This disparity in the blood flow to the appendage and nonappendage regions suggests that the appendage plays an augmented hemodynamic role during exercise, thus requiring a larger proportion of the nutrient flow.

We monitored an index of coronary vascular resistance (mean aortic pressure/mean coronary flow) in 19 heart-blocked conscious dogs paced at 60 beats/min and instrumented with an aortic pressure catheter, left circumflex artery electromagnetic flow probe, and a coronary occluder. Cessation of pacing for a single beat resulted in a long diastole control (LDC) intervention beat of 2-second duration characterized by a progressive rise in diastolic coronary vascular resistance index. A 400-msec coronary artery occlusion early in a long diastole (LD4) dramatically inhibited the rate of rise in resistance index during the first 600 msec (phase 1) after occlusion. Partial recovery of the resistance index rise rate was evident during the remaining 400 msec (phase 2) of the long diastole. In nine dogs, LDC and LD4 intervention beats were instituted during two conditions of myocardial metabolic activity in which the myogenic stimuli associated with coronary occlusion would be similar: 1) paired pacing and 2) normal pacing plus intravenous adenosine and phenylephrine infusions (AP) to maintain mean aortic pressure and coronary flow at paired pacing levels. During paired pacing, the LD4-LDC differences in phase 1 and 2 resistance index rise rates (-69 +/- 18 and -48 +/- 31 mmHg/ml/sec2, respectively) were greater than during normal pacing plus AP (-32 +/- 14 and -1 +/- 32 mm Hg/ml/sec2, phase 1 and 2, respectively) (p less than 0.05). These differences are consistent with operation of a metabolic mechanism in response to occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial oxygenation may be altered markedly by changes in tissue blood flow. During brief ischemia and reperfusion produced by transient occlusion of the left anterior descending artery in 10 open-chest dogs, changes in the oxygenation of tissue hemoglobin (Hb) plus myoglobin (Mb) and the oxidation-reduction (redox) state of mitochondrial cytochrome aa3 were monitored continuously using near-infrared spectroscopy. The nondestructive optical technique indicated that coronary occlusion produced an abrupt drop in tissue oxygen stores (tHb02 + Mb02), tissue blood volume (tBV), and the oxidation level of cytochrome aa3. Changes in the cytochrome oxidation state were related inversely to transmural collateral blood flow within the ischemic region (r = 0.77) measured with radiolabeled microspheres. Furthermore, there was a direct relationship (r = 0.91) between collateral blood flow and the tissue level of desaturated Hb and Mb (tHb + Mb). Reperfusion after 2 min of ischemia led to a synchronous overshoot of baseline in coronary flow and tBV followed by supranormal increases in tHb + Mb02 and the oxidation level of cytochrome aa3. The tHb + Mb level increased transiently during reperfusion. This response correlated inversely with collateral flow during ischemia (r = 0.91). Accordingly, the time required to reach peak tHb + Mb levels was shortest in dogs with high collateral flows (r = 0.75). Thus collateral blood flow partially sustains myocardial oxygenation during coronary artery occlusion and influences tissue reoxygenation early during reperfusion.

Compliance of the left atrial chamber was estimated with and without the appendage intact in six isolated canine left atria. Pressure-volume determinations were measured over a range of 5-30 mmHg for the whole left atrium and were repeated with the appendage excluded. The slope of the pressure vs. normalized volume data for the left atrium without the appendage (10.45 +/- 0.87) was significantly greater (P less than 0.01) than with the appendage intact (4.10 +/- 0.72). These data suggest that the left atrial appendage is more compliant than the remaining left atrium. Assuming that this relationship remains in vivo, the left atrial appendage may play an augmented role in maintaining hemodynamic function when filling pressures are elevated.

In this study, three tests of computer ECG analysis function were conducted: 1) interpretation of serial tracings using the single record analysis program, i.e. without serial comparisons; 2) interpretation of the same tracings using a computer-comparison program; and 3) interpretation of these tracings using not only a computer-comparison program but also an editing program which allows amending of each serial record and insertion of any corrections into the computer data base before the next comparison. There was an over-all reduction of 84% in the number of statement changes needed to produce a correct final report by using the combined comparison and editing program. When this combined program was used, 81% of all computer interpretations required no alteration, --a considerable saving of time in analyzing serial electrocardiographic tracings. Serial comparison was required in in 27--45% of all ECG's taken in four medical centers.

This study was undertaken to determine whether adenosine release from myocardial cells plays a role in coronary reactive and functional vasomotion. Reactive hyperaemic blood flow responses to 10 s complete occlusions and 400 ms diastolic occlusions of the left circumflex coronary artery and to the vasomotor responses to the increased cardiac demand following ventricular extra-activation were examined in a chronic, heart-blocked dog preparation during a control period and following intravenous bolus administration of aminophylline (5 mg X kg-1). Aminophylline administration resulted in a 19% decrease in the blood flow debt repayment ratio of 10 s reactive hyperaemic responses compared with the control period. However, administration of aminophylline had no effect on the coronary vascular response to 400 ms diastolic occlusions or to ventricular extra-activations. These observations indicate that adenosine may play a role in the coronary vascular response to prolonged interventions but that other factors, as yet unidentified, may be implicated in the beat-to-beat regulation of coronary vascular resistance.

Studies were conducted to determine the effects of adenosine on transmural myocardial blood flow distribution. Both maximal and submaximal vasodilatory doses of adenosine were infused into awake resting dogs chronically instrumented with coronary flow probes and aortic and left atrial pressure catheters. Radioactive microspheres (8-10 micron) were used to determine regional coronary blood flow. Four experimental protocols were evaluated: 1) the effects of maximal (1.00 mg . kg-1 . min-1) as well as submaximal (0.45 mg . kg-1 . min-1) vasodilatory levels of adenosine, 2) the dose-response characteristics of adenosine, 3) the dose-response characteristics of dipyridamole, and 4) the effects of adenosine in the presence of an increased arterial PO2. The data indicate that maximal vasodilatory doses of adenosine have little effect on the endocardial-to-epicardial blood flow ratio, whereas submaximal doses result in a marked preferential endocardial perfusion. This relative increase in endocardial perfusion was not altered by hyperoxia. Dipyridamole, in submaximal doses, produced a similar preferential flow to the endocardial layer. These data demonstrate that the vasodilator reactivity to adenosine infusion is greater in the endocardial layer,

Hemodynamic and regional myocardial blood flow responses were studied 5 seconds (early) and 30 seconds (late) after abrupt proximal aortic constriction in chronically instrumented awake dogs. During the early phase, left ventricular end-diastolic pressure (LVEDP) increased and stroke volume (SV) decreased significantly. During the late phase, there was a positive inotropic response manifested by a decrease in LVEDP and increase in SV (Anrep effect). The late inotropic response was closely associated with a recovery from subendocardial underperfusion. Hemodynamic and regional flow responses after beta-adrenergic blockade with propranolol (0.4 mg/kg) were similar to those observed during control. Studies during coronary vasodilation induced by adenosine (0.75--1.0 mg/kg per minute) showed that, if subendocardial flow was elevated during the early phase, the early increase of LVEDP and decrease of SV were less than control; however, if subendocardial flow did not change from control in the early phase and did not subsequently increase, there was no late inotropic response. These data suggest that the Anrep effect in the awake dog is closely related to a recovery from subendocardial ischemia.

A cannulation technique for creating a nonobstructive port in a proximal coronary artery is described. The use of this technique in awake animals allows the blood pressure to be measured in a coronary artery distal to an experimentally produced stenosis. This port can also be used to inject drugs directly into the coronary bed.

Conductance of the coronary collateral circulation during the course of two abrupt circumflex coronary occlusions (pre- and posttreatment with nitroglycerin) was measured in awake dogs approximately 2 wk after collateral vessels were stimulated to develop. The pressure gradient from the central aorta to the distal circumflex coronary artery was measured, and myocardial blood flow was determined by 9-microns radioactive microspheres at 30 s and 4 min after coronary occlusions. Collateral conductance was calculated as mean collateral blood flow divided by the mean aorta-coronary pressure gradient. Before nitroglycerin, collateral conductance increased in all eight dogs from 30 s to 4 min by a mean value of 0.006 +/- 0.003 ml.min-1.g-1.mmHg-1. After nitroglycerin administration, the conductance at 30 s increased from the prenitroglycerin control value of 0.009 +/- 0.008 to 0.014 +/- 0.012 ml.min-1.g-1.mmHg-1, P less than 0.03. The mean change in conductance from 30 s to 4 min postnitroglycerin 0.003 +/- 0.003 ml.min-1.g-1.mmHg-1 was significantly less than during prenitroglycerin (P = 0.01). These data indicate that an increase in conductance during coronary occlusion occurs even in the immature collateral circulation. This effect presumably takes place in the arterial smooth muscle at the origin of the collateral vasculature.

Chronically instrumented awake dogs were used to study the effects of nitroglycerin and propranolol on the transmural distribution of myocardial blood flow during transient ischemia. Studies were carried out 7-14 d after implantation of an electromagnetic flowmeter probe and balloon occluder on the left circumflex coronary artery, placement of epicardial minor axis sonar crystals, and implantation of left atrial, left ventricular, and aortic catheters. The occluder was inflated to completely interrupt flow for 10 s followed by partial release to reestablish flow at 60% of the preocclusion level. During this partial release, which served as the control for the study, regional myocardial blood flow was measured with 7- to 10-mum radioactive microspheres. After control measurements, seven dogs were given nitroglycerin (0.4 mg i.v.) and eight dogs propranolol (0.2 mg/kg i.v.). 5 min later the occlusion and partial release sequence was repeated, and regional myocardial blood flow was measured when heart rate, aortic and left ventricular end-diastolic pressure, and minor axis diameter were unchanged from control values.The data values were selected so that total flow to the ischemic region during partial release after nitroglycerin or propranolol administration was not significantly different from flow during the control partial release. After nitroglycerin administration, endocardial flow (endo) in the ischemic region increased from 0.46+/-0.07 to 0.59+/-0.06 ml/min per g (P < 0.006); epicardial flow (epi) decreased from 0.78+/-0.09 to 0.70+/-0.08 ml/min per g (P < 0.04). The endo:epi ratio increased from 0.65+/-0.07 to 0.92+/-0.10 (P < 0.05). In contrast, administration of propranolol produced no significant change in transmural flow (endo, 0.42+/-0.02 and 0.46+/-0.03 ml/min per g; epi, 0.71+/-0.06 and 0.70+/-0.07 ml/min per g) or in the endo:epi ratio (0.60+/-0.03, 0.66+/-0.06) in the ischemic region. Nitroglycerin and propranolol produce different effects on the transmural distribution of blood flow to ischemic myocardium. Nitroglycerin can increase blood flow to the underperfused endocardium in the absence of alterations in heart size, hemodynamic parameters, and total transmural flow to the ischemic region. Under similar conditions, propranolol has no significant effect on the transmural distribution of blood flow to an ischemic region.

The purpose of this study was to determine whether coronary collateral blood flow changes in response to repeated brief periods of ischemia in dogs in which no attempt has been made to stimulate collateral vessel development. The dogs were instrumented with aortic and left atrial catheters and a balloon occluder on the left circumflex coronary artery and were studied in the awake state the following day. Blood flow to the collateral dependent myocardium was measured using 9 mu radioactive microspheres during four coronary occlusions of two minutes duration, each separated by one hour of reperfusion. A small but statistically significant increase in mean collateral blood flow was noted between the first and fourth occlusions; .03 to .05 ml/min/g. These data suggest that transient periods of brief ischemia may result in increases in collateral blood flow.

A reproducible model for the production of moderate to severe concentric left ventricular hypertrophy has been developed in this laboratory. Coarctation-banding of the ascending aorta was performed successfully in 10 puppies. There were no late deaths related to aortic rupture, and in the dogs surviving for 1 yr no evidence of congestive heart failure was present. A second operative procedure was performed in seven dogs for chronic instrumentation, and all survived. Severe supravalvular aortic stenosis with a marked peak systolic pressure gradient was noted in each dog. Postmortem examination revealed a substantial increase in left ventricular mass and in the ratio of left ventricular to body weight.

Concentric left ventricular hypertrophy was produced in puppies by coarctation banding of the aorta at age 7 weeks. Hemodynamic, morphologic and biochemical studies were carried out 18 months after the operation. Systolic blood pressure proximal to the aortic constriction was 216 +/- 16 mmHg in experimental dogs compared with 115 +/- 5 mmHg in littermate control dogs. Ejection fraction of control and experimental dogs were 59 +/- 4 and 64 +/- 7, respectively. The left ventricular end-diastolic pressure was 6.0 +/- 0.4 in control and 8.4 +/- 1.1 in experimental dogs. There was no sign of overt heart failure in the experimental dogs. Anatomical analysis of different regions of the heart indicated that LV mass in the experimental dogs was increased by about 60%. Ultrastructure of mitochondria in situ, as observed under electron microscope, was normal both in control and hypertrophic hearts. Mitochondria isolated from epicardial and endocardial regions of the stable hypertrophic hearts showed normal rates of respiration, phosphorylation, citrate synthase, and cytochrome c oxidase activities compared to those isolated from hearts of littermate control dogs. It was, therefore, concluded that mitochondrial function is adequately preserved to meet the increased demand for energy in this model of stable cardiac hypertrophy of long duration.

The dynamic geometry of the left ventricle was assessed with the use of chronically implanted pulse-transit ultrasonic dimension transducers. The orientation of the transducers allowed the measurement of left ventricular minor and major axis diameters and equatorial wall thickness in the conscious dog. The left ventricle was modeled as a three-dimensional, prolate ellipsoidal shell. Left ventricular and pleural pressures were measured with high fidelity micromanometers. Aortic blood flow was obtained with electromagnetic flow probes. To test the assumptions inherent in this technique, left ventricular mass, internal volume, stroke volume, and peak aortic flow were computed from the dimension data and compared to directly measured values. Correlation coefficients of 0.95 or greater were obtained for each of these comparisons. In addition, the calculated left ventricular mass was constant to within +/- 6% of the mean value throughout the cardiac cycle. We found that the dynamic contraction pattern of the left ventricle was dependent on the physiological state of the dog. Furthermore, in the conscious state, shortening of the minor axis diameter, lengthening of the major axis diameter, and slight thickening or thinning of the wall were noted during isovolumic contraction (isovolumic ellipticalization pattern). In the open-chested, anesthetized state, however, marked rearrangements in geometry were observed during isovolumic contraction manifested by lengthening of the minor axis diameter, and significant thickening of the wall (isovolumic sphericalization pattern). We also observed that left ventricular volume was significantly diminished in the open-chested state. The isovolumic contraction pattern in open-chested dogs could be changed from sphericalization to ellipticalization by increasing end-diastolic volume with the infusion of saline. During a vena caval occlusion in the conscious state, the contraction pattern changed from isovolumic ellipticalization to isovolumic sphericalization as the end-diastolic volume decreased. Thus, the exact pattern of left ventricular contraction was found to be a function of left ventricular volume.

The objectives of this study were to test the hypothesis in awake dogs that during control conditions endocardial vessels are maximally dilated and to determine whether variables introduced by general anesthesia and thoracotomy modify distribution of myocardial blood flow or impair capacity for augmentation of flow in response to a coronary vasodilator stimulus. Myocardial blood flow was measured in relatively small, 2-3 g, left ventricular epicardial and endocardial samples by using 7-10-mum radioisotope-labeled microspheres during control conditions and during infusion of adenosine in dosages which produced maximum increases in coronary blood flow. Measurements were made initially in awake resting animals and were repeated after pentobarbital anesthesia, thoracotomy, and pericardiotomy. Blood flow (mean+/-SEM) in the epicardium and endocardium, respectively, was 0.75+/-0.06 and 0.83+/-0.06 during control conditions and 4.98+/-0.28 and 4.49+/-0.27 cm(3)/min/g during adenosine. These data demonstrate considerable capacity for vasodilation in both myocardial layers and thus refute the hypothesis that endocardial vessels are maximally dilated during control conditions. During control conditions blood flow within epicardial and endocardial layers was essentially homogeneous around the circumference of the left ventricle. In contrast to previous studies in anesthetized animals, however, transmural gradients were present in most regions, i.e., endocardium: epicardium ratio (endo/epi) 1.06-1.16. During adenosine, circumferential epicardial flows were homogeneous; however, circumferential endocardial flows were inhomogeneous and increased less than epicardial flows, endo/epi 0.81-0.99.Anesthesia, thoracotomy, and pericardiotomy increased epicardial and endocardial flow, mean values 1.08+/-0.10 and 1.11+/-0.08 cm(3)/min/g, respectively. Transmural gradients remained in only papillary muscle regions. Adenosine increased epicardial flow comparably before and after anesthesia. Although adenosine increased endocardial flow three- to fourfold after anesthesia, the increase was considerably less than epicardial flow, i.e., endo/epi 0.63-0.78.

This study was designed to examine local effects of acute cellular injury on regional myocardial blood flow. Studies were carried out in awake dogs chronically prepared with indwelling catheters in the aorta and left atrium and an occluder on the left circumflex coronary artery. Regional myocardial blood flow was measured by using 7-10-mum radioisotope-labeled microspheres after reestablishing inflow to a region subjected to a 2-h complete coronary occlusion. Microspheres were injected 15 s, 15 min, 4 h, and 3 days after reperfusion to assess effects of cell injury at varying intervals after reperfusion. Effects of acute cellular injury on blood flow were assessed by determining the relationship between regional blood flow and the extent of subsequent cellular necrosis measured in multiple tissue samples, weight 1-2 g, from the entire ischemic zone. The extent of cellular necrosis was determined from histological sections of each tissue sample. Prolonged ischemia effected local tissue responses which altered perfusion as a function of the interval after reperfusion and the subsequent extent of myocardial necrosis. Although the net response in each region immediately after reperfusion was vasodilation, the hyperemia in regions which subsequently suffered cellular necrosis was attenuated in direct proportion to the extent of subsequent infarction. Blood flow to acutely injured regions remained equal to, or in excess of, flow to nonischemic regions 15 min after reperfusion, but at 4 h and 3 days after reperfusion, flow was significantly decreased in regions with greater than 50% infarction. Thus, these data indicate that prolonged ischemia initiates tissue responses which progressively reduce myocardial perfusion after reperfusion. These effects on tissue perfusion may result from normal responses to irreversible injury and (or) abnormal responses to reversible and thus, potentially alterable, ischemic injury.

Vectorcardiograms (VCG) from a consecutive group of 77 patients with significant aortic valve disease were analyzed. All of the patients had complete left and right heart catheterization with normal coronary arteriograms and normal left ventricular contraction. Thirty-five (46%) patients met VCG criteria for anterior myocardial infarction (AMI-35%) and/or inferior myocardial infarction (IMI-14%). This was a significant increase in false positive diagnosis for both criteria compared to a group of 200 normal volunteers under age 30 and 100 patients with normal hearts by cardiac catheterization (P less than 0.01). It was found that if the VCG diagnosis of myocardial infarction was deferred when the maximal transverse plane magnitude was greater than 1.9 mV, the incidence of AMI false positive diagnosis decreased to 3% and the incidence of IMI false positive diagnosis decreased to 1%. The same rule was applied to the aortic valve disease cohort, a group of 124 patients with documented AMI and a group of 158 patients with IMI. This decreased the sensitivity of the AMI criteria from 93 to 83% and of the IMI criteria from 85 to 77%. The increase in average performance was statistically significant fro the AMI criteria (P less than 0.05) but not for the IMI criteria.

This study was undertaken to examine the independent effects of atrial tachycardia, ventricular tachycardia, and atrial fibrillation (AF) on atrial and ventricular blood flow in conscious, heart-blocked dogs using radioactive microspheres. Atrial blood flow averaged 0.54 +/- 0.08 ml/min/g during the control period at an atrial rate of 124 beats/min and a ventricular rate of 90 beats/min. Atrial flow increased to 0.72 +/- 0.12 ml/min/g during atrial pacing at 236 beats/min, but was not significantly altered by ventricular pacing at 200 beats/min. AF at a ventricular rate of 90 beats/min resulted in atrial flow values of 0.91 +/- 0.08 ml/min/g. The ratio of atrial flow to left ventricular flow during AF averaged 1.18 +/- 0.08. Administration of a maximal vasodilating dose of adenosine during AF further increased atrial flow to 2.18 +/- 0.16 ml/min/g. Atrial tachycardia or AF did not significantly affect ventricular blood flow. These data indicate (1) that atrial blood flow increases significantly during AF, reaching flow values per gram of tissue comparable to those of the left ventricle, and (2) that this flow is regulated by the metabolic needs of the atrial tissue and does not represent maximal vasodilation.

Measurements of cerebral spinal fluid pressure, arterial pressure, and internal carotid artery blood flow were obtained in a series of patients during a Valsalva maneuver. During straining (phase II), an 11% reduction in mean arterial pressure was associated with a 21% decrease in internal carotid flow from control values; and following release (phase IV), the 19% increase in mean arterial pressure produced a 22% increase in internal carotid artery flow. Perfusion pressure computed as the mean arterial pressure minus cerebral spinal fluid pressure and internal carotid artery blood flow were used to calculate an index of cerebral vascular resistance. The data indicate that a modest but significant decrease in vascular resistance occurred during phases II and III followed by return to control levels during phase IV. These changes in vascular resistance were not rapid enough or of sufficient magnitude to maintain constant cerebral perfusion during the Valsalva maneuver.

The Animal Models for Protecting Ischemic Myocardium Study was undertaken for the purpose of developing reproducible animal models that could be used to assess interventions designed to limit infarct size. This paper describes the results obtained in an unconscious dog model and in a conscious dog model, developed in three participating laboratories. The unconscious dog model, involving reperfusion after 3 hours of ischemia in open-chest dogs, was intended to determine whether therapy followed by early reperfusion would limit infarct size more than reperfusion alone. The conscious dog model used chronically instrumented dogs and permanent coronary occlusion to better mimic myocardial infarction in man. In both models, the proximal circumflex artery was occluded, and the primary experimental endpoint was infarct size, as measured by histological techniques 3 days after the initial occlusion. Infarct size was analyzed in relation to baseline variables including the anatomic area at risk, collateral blood flow to the subepicardial zone of ischemia and hemodynamic determinants of myocardial metabolic demand. Most of the variation in infarct size in control dogs could be related to variation in the area at risk, collateral blood flow, and rate pressure product. Using multivariate analysis and groups of 15 dogs, an intervention that limited infarct size by 10-13% of the area at risk would have been detected 50% of the time. Larger treatment effects would be detected more readily, and smaller effects often would be missed, unless group sizes were larger. Two drugs, verapamil and ibuprofen, were evaluated in both models, with experimental group sizes averaging 13 and 20 dogs, in the unconscious and conscious models, respectively. Three of 15 verapamil-treated dogs in the unconscious model study had much smaller infarcts than expected from baseline parameters. With these exceptions, neither drug limited infarct size in either model.

The purpose of this study was to correlate dimensions and transmural blood flow in a segment of myocardium supplied by a coronary artery undergoing gradual closure. Nine adult dogs were instrumented with an electromagnetic flow probe, pneumatic occluder, and an ameroid constrictor on the circumflex coronary artery. Ultrasonic crystals were implanted 10 mm from the external surface of the left ventricle in a segment perfused by the circumflex artery. Regional blood flow was determined with 7- to 10-microns radiolabeled microspheres. Data were collected in the awake state at rest before closure began (control), during partial closure, and immediately after total closure. Seven of the nine animals were studied after occlusion during treadmill exercise. During both partial and total closure at rest the rate and extent of systolic shortening as well as the transmural blood flow were unchanged from control. During treadmill exercise mean flow increased. However, flow was redistributed away from the inner two layers causing deterioration in both the rate and extent of shortening of this segment. These data suggest that, although regional myocardial function and flow can be maintained at rest by the immature canine collateral circulation, these parameters are impaired markedly during augmented flow with exercise.

1. Coronary insufficiency is a pathophysiologic state that can initiate lethal cardiac arrhythmias in the absence of myocardial necrosis. Patients with suspected coronary insufficiency should be monitored until they are stabilized and a diagnosis is confirmed. 2. Early and adequate intravenous antiarrhythmic prophylaxis with lidocaine to raise the fibrillation threshold in the setting of coronary insufficiency can prevent primary ventricular fibrillation. Classic "warning arrhythmias" are not predictive of ventricular fibrillation. Their persistence during adequate antifibrillatory prophylaxis does not indicate therapeutic failure. 3. The isoenzyme of creatine phosphokinase, CPK-MB, is an extremely sensitive and specific indicator of myocardial necrosis if measured serially during the 24 hours following the onset of symptoms suggesting coronary insufficiency. It may prove most useful in eliminating the false positive diagnosis of myocardial infarction in difficult clinical cases. 4. The management of heart failure in myocardial infarction requires an understanding of the relationship between ventricular preload and the cardiac output. The treatment of clinical manifestations of an elevated ventricular preload in asymptomatic patients is not justified and may be detrimental. In symptomatic patients, however, judicious manipulation of ventricular preload should be the first therapeutic consideration, and an optimal filling pressure should be achieved and maintained when other determinants of the cardiac output are manipulated. 5. Indications for the prophylactic insertion of a temporary transvenous pacing electrode for heart block associated with myocardial infarction must be individualized. Most authorities agree that prophylactic pacing may be justified in patients with evidence of new infranodal block involving two of the three fascicles. Patients with bifascicular block who progress to complete heart block transiently may benefit from permanent transvenous pacemaker insertion before discharge. 6. Hospitalized patients with persistent pain of suspected cardiac origin but without evidence of myocardial infarction can be studied safely with coronary angiography. A small percentage will be normal or have diffuse disease that is inoperable. Of those with operable disease, short-term mortality appears to be similar for medical and surgical therapy. 7. Patients with an uncomplicated myocardial infarction may be safely discharged from thehospital by day 7-10. 8. Experimental evidence indicates that modification of infarct size is possible. Application of these concepts to human subjects presently is limited by the absence of a proved method of measuring infarct size in vivo in humans.