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As cardiopulmonary bypass is frequently accompanied by hypotension, the effect of varying perfusion pressure (30, 60, and 90 mm Hg) on the adequacy and distribution of coronary flow was studied under conditions of a normothermic beating empty state, of normal and hypertrophied hearts of 20 mongrel dogs, using the radioactive microsphere technique. In the normal hearts, 30 mmHg caused a 47% (P < 0.005 to prebypass) reduction of left ventricular coronary flow but did not change flow distribution (ENDO/EPI flow ratio: 1.01); increasing mean perfusion pressure from 30 to 90 mm Hg did not alter the oxygen consumption but did increase the coronary flow and decrease the oxygen extraction ratio. In the hypertrophied hearts, 30 and 60 mm Hg perfusion pressures resulted in a redistribution of flow away from the subendocardium (ENDO/EPI flow ratio: 0.82 and 0.87, respectively, P < 0.02 to prebypass). An increase in perfusion pressure from 30 to 60 mm Hg resulted in a significant increase in oxygen uptake (4.0 vs 5.6 cc/100 g/min, respectively, P < 0.02). An increased perfusion pressure of 90 mmHg resulted in a sufficient subendocardial flow and an augmentation of the oxygen uptake. These results indicate that subendocardial underperfusion occurs in the beating empty hypertrophied heart, under conditions of lower perfusion pressures (30 and 60 mm Hg), but that such can be improved by increasing the perfusion pressure to 90 mmHg. In contrast, the subendocardial underperfusion does not occur with a perfusion pressure of 30 mm Hg in normal hearts.

The effects of chronic instrumentation on regional myocardial performance and regional myocardial blood flow were studied in 8 mongrel dogs. Regional segment lengths were measured by an ultrasonic dimension gauge technique at two areas of the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX). Regional myocardial blood flow was measured by a tracer microsphere technique. These measurements were repeated while the animals were conscious on the 4th, 11th, 21st and 28th days after instrumentation. On the 4th day, the heart rate was rather high and regional shortening at both the LAD and LCX areas remained suppressed. After the 11th day, hemodynamic variables such as heart rate, left ventricular pressure and regional wall motion were fairly constant. Regional myocardial blood flow and its distribution were also constant throughout the experimental period. Fibrosis of the epicardium invariably induced by surgical procedures did not affect the distribution of regional blood flow as compared with that of the interventricular septum. Thus, a stable hemodynamic state was recorded after the 11th day following surgical manipulation and the implantation of sensors and catheters did not affect the level of regional myocardial blood flow or its distribution at rest. Such long term reproducible measurements of regional wall motion and regional myocardial blood flow may facilitate chronic studies of cardiovascular physiology.

Summary Front surface fluorometry and porcine coronary arterial strips loaded with fura-2 were used to investigate the effect of endothelin on cytosolic Ca concentrations, [Ca]i, and on contractile force, the objective being to elucidate the mechanism of action. Both in the presence and absence of extracellular Ca, endothelin induced rapid and dose-dependent increases in [Ca]i and in contraction. When caffeine-sensitive and histamine-sensitive intracellular Ca stores were depleted, in Ca-free medium, a transient contraction but no increase in [Ca]i followed the subsequent application of endothelin. This Ca-independent component was largely inhibited by the relative protein kinase C inhibitor, H-7, but not inhibited by W-7, calmodulin antagonist. This component is probably linked to activation of protein kinase C.

Effects of beta-adrenergic blockade on regional myocardial dysfunction induced by coronary artery occlusion were studied in chronically instrumented, conscious dogs before (n = 8) and after (n = 7) collateral development. Intravenous atenolol or propranolol produced no beneficial effects on systolic shortening in the area rendered ischemic during 2 minutes of circumflex occlusion, before collateral development. After the collateral development by repetitive 2-minute coronary occlusions, regional asynergy recovered to the preocclusive level during 2 minutes of occlusion. Both atenolol and propranolol significantly improved the peak reductions of regional shortening by 19 +/- 9% and 18 +/- 9%, respectively (p less than 0.05 versus without beta-blockade). These beneficial actions of beta-blockade were again noted during atrial tachypacing at matched heart rates of 160 +/- 11 beats/min. Thus the beneficial effects of beta-blockade on regional asynergy during coronary occlusion depend on the level of functional state of the collaterals and cannot be totally accounted for by the reduction in heart rate or by the cardioselectivity.

An abnormal echocardiographic signal was detected in the myocardium on the echocardiographic examination of the septum and posterior left ventricular wall in a patient found to have lymphosarcoma which was diffusely infiltrated in the myocardium. This echocardiographic abnormality was well correlated with the autopsy findings. Echocardiography appears to be one of useful methods in diagnosing cardiac mural tumor antemortemly.

Two-dimensional echocardiography has recently facilitated production of cardiac sectional images. This paper describes a method to estimate volumes and surface areas of various cardiac regions from their oblique sectional images. Cardiac oblique sectional images are recorded with a sector scanner probe which is tilted gradually on an intercostal point. The contour of a particular region on the recorded image is traced manually to put into a computer. The computer calculates the volume and the surface area using a triangular pyramid as the fundamental segment. The accuracy on this calculation method was evaluated by two types of phantoms constructed in the computer. The method is applicable to determine the volume and the surface area not only of the heart, but also of other organs even though they have indents or protrusions on the surface.

Of 383 patients with vasospastic angina who were followed for a period of 3.2 +/- 0.1 years, 9 (2%) died suddenly from cardiac causes. Calcium antagonists had been given to 98% of our patients. Only one patient who died suddenly had a fixed coronary stenosis of 75% or greater. Eight of the 9 patients showed ST segment elevation during anginal attack at rest, and 3 patients showed ST segment elevation at both anterior and inferior leads. Sudden death occurred in 6 of 41 patients (12.5%) who were documented to have multivessel coronary spasm, but in only 3 of 342 patients (1%) who had single vessel spasm (p less than 0.01). Serious arrhythmia occurred during anginal episode in 3 of 9 patients who died suddenly (53%) and in 52 of 374 who did not (14%). These results suggest that the frequency of sudden cardiac death was rather low in Japanese patients with vasospastic angina. The risk of sudden death was increased in patients with multivessel spasm and serious arrhythmia during anginal attacks but not these with fixed coronary stenosis.

This report describes a case with flail right and noncoronary cusps due to bacterial endocarditis, diagnosed with real-time two-dimensional echocardiography. Real-time two-dimensional phased array sector scanner demonstrated 2 cugdel-shaped lesions in the region of the left ventricular outflow tract through the aortic root, pendulating upward and downward floating along the blood stream. This study shows that the real-time two-dimensional echocardiography is a very useful noninvasive tool in the early diagnosis of flail aortic valve.

Effects of pertussis toxin on Ca2+ transients in rat arterial smooth muscle cells in primary culture were monitored, using quin 2-microfluorometry. In the presence or the absence of extracellular Ca2+, norepinephrine, histamine, caffeine and high extracellular K+ induced elevations in cytosolic Ca2+ concentration. Cytosolic Ca2+ elevations induced by norepinephrine and histamine were inhibited by pretreatment of the cells with pertussis toxin, time- and dose-dependently. However, elevations induced by caffeine and K+-depolarization were unaffected by the pretreatment with this toxin. Thus, it is suggested that GTP binding protein, a pertussis toxin substrate and involved in the receptor-mediated cytosolic Ca2+ transients, is not involved in transient elevations in cytosolic Ca2+ induced by caffeine and K+-depolarization in cultured vascular smooth muscle cells.

The baroreflex control of vascular resistance and heart rate was studied in 11 patients to determine whether it is impaired in patients with acute myocardial infarction. Reflex forearm vasoconstriction in response to lower body negative pressure at 40 mm Hg was less in the early convalescent phase (mean seven days) than in the late convalescent phase (mean 41 days). Pressor as well as vasoconstricting responses to the cold pressor test did not differ between the early and late convalescent phases. The slope of the regression line relating systolic blood pressure and the RR interval during a transient rise in blood pressure produced by intravenous phenylephrine was appreciably reduced in the early convalescent phase of myocardial infarction. These results suggest that baroreflex control of vascular resistance and heart rate is impaired in patients with acute myocardial infarction.

Effects of leukotriene (LT) C4 and LTD4 on coronary artery spasm in atherosclerotic miniature pigs were examined angiographically. Endothelial balloon denudation of the left circumflex coronary artery was performed in 15 Göttingen miniature pigs; 11 were fed a 2% cholesterol diet and four were fed a regular diet for 3 months. Three months after this denudation, the area of the coronary artery was reduced by 94 +/- 2% and 43 +/- 5% (p less than .01) in the denuded and nondenuded areas by the intracoronary administration of 10 micrograms/kg histamine after pretreatment with 60 mg/kg iv cimetidine. The effects of LTC4 and LTD4 on coronary diameter and the preventive effects of FPL-55712, a LTC4 and LTD4-receptor blocker, or diphenhydramine, a histamine H1-receptor blocker, on histamine-induced coronary spasm were then examined angiographically. Administration of LTC4 or LTD4 in doses of 1 and 10 micrograms into the left coronary artery, or selectively into the left circumflex and left anterior descending coronary arteries in a dose of 5 micrograms, led to the elevations in the ST segment on the electrocardiogram and there was delayed filling of the contrast medium in the peripheral coronary artery. However, these LTs provoked no augmented constrictions at any site on the epicardial coronary arteries (n = 15). Diphenhydramine, 1 mg/kg (n = 6), abolished the histamine-induced coronary spasm FPL-55712, 0.1 mg/kg, with which the LT-induced myocardial ischemia was abolished, did not prevent the histamine-induced coronary artery spasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty-seven normal rats were used to investigate the effect of ATP on Rb86 clearance of the various organs. Blood pressure was decreased by intravenous bolus injection of 10 or 50μgATP/Kg body weight (b.w.). In 10μgATP/Kgb.w. infusion, Rb86 clearance of the heart, liver, and pancreas was increased by 43, 29, and 27% respectively. In 50μgATP/Kgb.w. infusion which reduced the arterial blood pressure strikingly, Rb86 clearance of the liver and pancreas was increased; and that of the kidney was decreased significantly. The present study may suggest that the effective nutritional blood flow of the heart, liver, and pancreas is increased by intravenous infusion of 10μgATP/Kgb.w.

A decreased diastolic slope (EF slope) of the tricuspid valve on the M-mode echocardiogram may not indicate the presence of tricuspid stenosis (TS). To explore diagnostic echocardiographic signs of TS, we examined an M-mode and 2-dimensional (2-D) echocardiogram in 9 patients with documented TS of rheumatic origin and in 14 patients with rheumatic heart disease who showed a decreased EF slope (less than 40 mm/s) but did not have TS. By M-mode echocardiography, the EF slope was not different between patients with TS (24.4 +/- 2.2 mm/s) and those without TS (27.4 +/- 2.0 mm/s). The early diastolic excursion (DE amplitude) of the tricuspid valve was significantly lower (p less than 0.001) in patients with TS (7.6 +/- 1.0 mm) than in patients without TS (13.9 +/- 0.6 mm). Two-dimensional echocardiograms of the tricuspid valve revealed diastolic doming in all patients with TS. Diastolic doming of the tricuspid valve was detected most often (all of 7 patients) in the apical 4-chamber view. In contrast, no patients without TS who had a decreased EF slope on the M-mode echocardiogram showed diastolic doming. These data suggest that a reduced DE amplitude of less than or equal to 10 mm associated with a decreased EF slope on the M-mode echocardiogram and diastolic doming of the tricuspid valve on the 2-D echocardiogram are useful echocardiographic signs in the diagnosis of TS.

Regional wall motion was analyzed to deduce the muscle property unique to regional contractile states. End-systolic pressure length relations were evaluated under global changes in a contractile state, under selective intracoronary administration of inotropic agents to produce regional hypo- or hyper-kinesis, and before and after extension of size of the ischemia. Linearity of the end-systolic pressure-length relation was confirmed in each perturbation; however, the behavior of this relation with regard to changes in the slope and X-axis intercept differed among the three situations. When the contractile state was altered globally by intravenous administration of inotropic agents such as dobutamine and propranolol, the slope of the end-systolic pressure-length relation changed in a manner similar to that seen with the pressure-volume relation or stress-strain relation, with no significant changes in the X-axis intercept. Namely, the level of global cardiac function determined the slope of the end-systolic pressure length relation. When regional hypokinesis was produced pharmacologically by selective intracoronary infusion of lidocaine, the X-axis intercept moved rightward, depending on the degree of regional hypokinesis. Expansion in the size of the ischemic area also shifted the X-axis intercept rightward. The latter two phenomena suggested that the hypokinetic segments were stretched by the surrounding intact myocardium. Accordingly, end-systolic pressure-length relations provide useful information concerning the functional state of regional myocardium. The systolic properties of the regional myocardium rendered hypokinetic have to be quantified so as to include the total geometry of the heart.

The precordial electrocardiographic map may be useful for non-invasive assessment of the extent of the acutely infarcted myocardium. Rapid and serial precordial electrocardiographic maps also may be useful to evaluate the effects of intervensions of drugs and efforts on the ischemic myocardium. In this study, the IBM-Bonner program was applied to produce a system for the precordial electrocardiographic map. Six electrodes at one intercostal space were moved in parallel from the second to the seventh intercostal space. Thus electrocardiograms (ECGs) could be recorded from 36 precordial sites, 6 × 6 matrix, and analyzed using the IBM-Bonner program. The measured values of the ECG waveform make feasible the automatic procurement of the precordial electrocardiographic map. Our mapping program can be used readily and anywhere the IBM-Bonner program is in use.

Previous studies have suggested that intravenous infusion of arginine vasopressin (AVP) inhibits sympathetic nerve activity (SNA) in rabbits by its action at the brainstem. This study aimed to determine, first, whether this action of AVP depended on functioning baroreflex mechanisms. The second aim was to determine the role of the nucleus tractus solitarii (NTS) in mediating this action of AVP. Experiments were performed in rabbits anesthetized with alpha-chloralose. Intravenous infusions of AVP (1, 3, and 10 mU/kg/min) resulted in progressive inhibition of renal SNA in rabbits with intact arterial baroreceptors and vagal afferents as well as in rabbits with sinoaortic denervation and bilateral vagotomy. The magnitudes of renal SNA inhibition evoked with AVP were comparable in the two groups. Renal SNA inhibition evoked with AVP at doses of 1 and 3 mU/kg/min in rabbits after sinoaortic denervation and vagotomy was totally blocked by chemical lesions with kainic acid of the bilateral NTS or the area postrema. Lesions of the NTS or the area postrema markedly attenuated (by about 60%) but did not totally block the response evoked with AVP at a dose of 10 mU/kg/min. AVP microinjected directly into the NTS did not evoke changes in renal SNA or arterial pressure, whereas AVP microinjected into the area postrema suppressed renal SNA. These results suggest that intravenous AVP at lower doses inhibited renal SNA by causing excitation of the NTS neurons, and this action of AVP did not depend on functioning baroreflex mechanisms. The second suggestion is that the NTS was unlikely to be the site where AVP directly interacted but instead received a neural connection, presumably from the area postrema, where AVP might directly interact.

The extent of myocardial infarction related to the pre-occlusive perfusion are was quantitatively evaluated in a canine model. The perfusion area was determined preocclusively by selective injection of tracer microspheres into the coronary artery in question, then the main trunk and a small lateral branch of the left circumflex coronary artery was occluded in group 1 (10 dogs) and group 2 (10 dogs), respectively. Rapid freezing was used to prepare autoradiographic samples for determination of the perfusion are along with samples for dehydrogenase staining in order to delineate the extent of myocardial infarction. The relationship between perfusion area and infarct size was examined in 50 micrometers thick samples from base, middle and apex of the ventricle and a direct linear correlation between the perfused (P) and infarcted area (I) in the left ventricle (LV) was noted regardless of the perfusion size or the location in the ventricle. The linear relationship I = 0.93P - 4.9 (r = 0.95, P less than 0.001) was obtained in all 20 dogs. Transmural extent of necrosis was larger in the endocardium than in the epicardium, thereby representing a more salvageable myocardium in the epicardium. It is concluded that the preocclusive determination of perfusion are by high resolution autoradiography is a useful method of obtaining physiological perfusion not affected by ischaemia. Also the infarct size when standardized by the perfusion area is mainly influenced by transmural location but not by the spacial geometry or the size of the occluded area.

The effect of collateral circulation on regional myocardial flow and wall motion of left ventricle was studied on 5 anesthetized dogs with a surgically implanted constrictor on the left circumflex coronary artery (LC). The grade of LC stenosis and wall motion of left ventricle (LV) were determined by cineangiography of the coronary artery and LV at the period of acute and chronic occlusion. Regional myocardial flow was determined by tracer microspheres (TM), labeled with four different isotopes, Sr85, Cr51, Sc46, Ce141. The first TM1 was infused after LC stenosis, TM2 during a temporary complete LC occlusion at the period of acute occlusion; TM3 and TM4 in a similar way 3 to 4 weeks after the acute LC stenosis. Three to four weeks after LC stenosis, i.e. chronic period of occlusion, the degree of LC stenosis progressed from 70--80% to 100% occlusion, but collateral flow and collateral vessels to the ischemic LC area were increased together with an improvement of wall motion of the ischemic LC area. The results may support the idea that collaterals may be an effective compensatory mechanism for ischemia. In contrast to an increase of collateral flow to the ischemic LV free wall in all five dogs, an increase to the posterior papillary muscle was found only in two out of five dogs.

A correlated study has been made of various divalent cations which are known to accelerate the formation of visible clots upon the addition of thrombin to fibrinogen. The experiments described demonstrate that calcium ions accelerate the aggregation of monomeric fibrin but have almost no effect upon the rate of release of fibrinopeptides from fibrinogen. On the contrary, magnesium ions do not accelerate the aggregation of monomeric fibrin but rather seem to accelerate the release of fibrinopeptides from the fibrinogen. The mechanism of the clot-promoting effect of various divalent cations probably differs from each other. The degree of the acceleration on aggregation caused by the mixtures of various divalent cations can be determined by the amount of the cation having the most potent accelerating effect in the mixtures.

A 37-year-old woman was admitted with an acute anterior myocardial infarction. Coronary arteriography revealed a dissecting aneurysm of the left main coronary artery. The patient died from perioperative myocardial infarction following aortocoronary bypass surgery on the 102nd hospital day. Histologic sections of the aneurysm revealed that granulation tissue had replaced the aneurysm, suggesting spontaneous healing of the dissecting aneurysm.

Responses of heart rate and blood pressure to transient myocardial ischemia were analyzed in patients with variant angina. Heart rate changes during ST segment elevation were examined by means of a Holter ECG monitoring system. All 27 ST segment elevations from 10 patients with anterior ischemia were accompanied by an increase in heart rate by 12 +/- 2 bpm (mean +/- SEM, p less than 0.001) at peak ST segment elevation. With inferior ischemia in nine patients, heart rate decreased significantly by 4 +/- 1 bpm (n = 28, p less than 0.001). However, 9 of these 28 ST segment elevations showed a biphasic response of heart rate, that is, an initial increase and subsequent decrease. Such heart rate changes were not different between ST segment elevations with and without chest pain. With chest pain systolic blood pressure rose in anterior ischemia by 42 +/- 5 mm Hg (n = 10, p less than 0.001) but fell in inferior ischemia by 22 +/- 8 mm Hg (n = 7, p less than 0.05). We conclude that a different cardiovascular reflex occurs in response to inferior versus anterior ischemia and it is independent of chest pain.

The reliability of five equations in assessing stroke volume from pulmonary artery pressure curves were critically evaluated in six dogs and in six patients. To alter stroke volume, isoproterenol, dobutamine, pro-pranolol, lactate Ringer solution and artificial pacing were employed in the animal study and diltiazem (a calcium blocker) in the human study. A good correlation was found between the calculated and measured stroke volume (r = 0.80–0.86 in the animal study and r = 0.94–0.96 in the human study). The assessment of stroke volume from the pulmonary arterial pressure curves using equations was as good as that from the aortic pressure curves calculated simultaneously. These results suggest that the five equations may be clinically applicable for assessing stroke volume in critically ill patients. The employment of pulmonary arterial pressure curves in assessing stroke volume may be more useful clinically since its recording can be carried out more safety than recordings of aortic pressure curves.

It is not known whether coronary vasospasm is associated with coronary thrombosis. In this study, plasma levels of fibrinopeptide A during anginal attacks in 24 patients with variant angina were examined. A hyperventilation test was used to induce angina. Hyperventilation induced angina and ST segment elevation (AST: 0.32 +/- 0.14 mV, p less than 0.01) in eight patients with variant angina. Fibrinopeptide A increased from 0.75 +/- 0.27 at control to 7.8 +/- 4.4 ng/ml (p less than 0.01) during anginal attacks in these eight patients. In addition, four patients had spontaneous attacks of angina; they also had elevated levels of fibrinopeptide A during attacks (from 2.0 +/- 1.2 at control to 21.9 +/- 18.0 ng/ml [p less than 0.01] during attacks). Hyperventilation did not induce either angina or ST segment elevation in 12 of the patients with variant angina. Fibrinopeptide A levels did not change with hyperventilation in these patients. To determine whether elevated plasma levels of fibrinopeptide A were associated with angina, the plasma levels of fibrinopeptide A were examined during exercise-induced angina in seven additional patients with stable effort angina. They all developed angina with treadmill exercise; however, plasma fibrinopeptide A did not change. Therefore, only the patients with variant angina demonstrated elevated levels of fibrinopeptide A during anginal attacks. These findings suggest that coronary vasospasm associated with myocardial ischemia may induce stasis of blood, resulting in fibrinogen-fibrin conversion in the coronary vessels.

Newly weaned male rats were maintained on a riboflavin-free diet for 5 weeks, and a study was made on the effect of the deficiency upon liver lipids. The content of glyceride in the livers varied among the deficient rats. High contents of glyceride were demonstrated in one-third of the deficient rats, whereas the similar level as that of control was shown in the remaining deficient rats. Contents of phospholipids and relative amounts of individual phospholipids were not altered significantly by the deficiency. Riboflavin deficiency exerted effects on fatty acid components of liver lipids. The composition of fatty acids of triglycerides varied in the deficient rats depending on the content of glycerides. However trends of increase in linoleic acid and decrease in palmitic acid towards fatty liver were observed in the deficiency in comparison with the control. On the other hand, the changes in phospholipid fatty acids were similar in all deficient rats, and the increase in linoleic acid and the decrease in arachidonic acid were brought about by the deficiency compared with controls, respectively. In liver homogenates, the incorporation of 14C-palmitate into triglycerides was higher in the deficient rats irrespective of the presence or absence of fluorde but incorporation into phospholipids was slightly lower in the deficient rats than in control animals.

We studied the subcellular distribution and the properties of [3H] mepyramine binding in the porcine vascular smooth muscle. A close correlation was observed between the specific binding activity of [3H] mepyramine and the extent of the enrichment of sarcolemmal marker enzyme in 4 subfractions obtained by sucrose density gradient centrifugation of the aortic microsome. In the binding isotherm in the sarcolemmal fractions from the aorta and coronary artery, there was no difference in the Kd value, but the Bmax of the coronary artery was significantly lower than that of the aorta. Thus, there is a single type of high affinity mepyramine binding site in the porcine vascular smooth muscle sarcolemma and the number of H1-receptors of the coronary artery may be smaller than that of the aorta.

The influence of graded perfusion pressure (30, 60, and 90 mmHg) at cardiopulmonary bypass were studied on beating empty hearts (BEH) or spontaneously fibrillating hearts (SFH) in the normothermic state. The adequacy and distribution of coronary flow and the myocardial oxygen consumption (MVO2) were examined using the tracer microsphere technique in twelve mongrel dogs. In the SFH, the left ventricular (LV) endocardium (ENDO)/epicardium (EPI) flow ratio indicated significant decrease at 30 and 60 mmHg (0.83 +/- 0.05 and 0.86 +/- 0.06, p less than 0.005, respectively), but was recovered to control value at 90 mmHg (1.01 +/- 0.13). In the BEH, these low perfusion pressures did not result in an abnormal flow distribution in the LV (1.03 +/- 0.03 at 30 mmHg). The flow distribution to the right ventricle (RV) relatively increased in both the BEH and the SFH (p less than 0.001). The ENDO/EPI ratio of the RV did not decrease at 30 mmHg in both groups (1.11 +/- 0.03 in BEH and 1.16 +/- 0.08 in SFH). Coronary blood flow and MVO2 were significantly higher in the SFH than in the BEH. Coronary blood flow increased significantly with increase in the perfusion pressure, in both groups. The MVO2 was constant in the BEH, regardless of the perfusion pressure, but increased in the SFH at increasing pressure. These results show that in the SFH, subendocardial underperfusion of the LV is induced at the perfusion pressure of 30 and 60 mmHg.

SUMMARY Recurrent ST-segment elevations inleads where new Q wavesdeveloped wererepeatedly recorded insixpatients during a recoveryphase ofacutemyocardial infarction. SuchST-segment elevations weretransient, occurred with orwithout chest pain, andreturned tocontrol levels. Noenzymatic changes signifying recurrent myocardial necrosis werefound after eachepisode. Selective coronarycineangiography in onepatient demonstrated a mildsegmental stenosis inthecoronaryartery perfusing theinfarcted area;this artery becamecompletely occluded after administration ofi.v. ergonovine. Administration ofcalcium antagonists effectively reduced thefrequency ofpostinfarction angina andST-segment elevations. Theclinical features suggest that thepostinfarction anginainthese patients isproduced bycoronaryarterial spasm andthat coronaryarterial spasm may causeseverelife-threatening dysrhythmias. SPONTANEOUSANGINAoccurs frequently inpatients withacutemyocardial infarction (AMI). Postinfarction angina isgenerally considered tobea poorprognostic sign because itmayresult inanextensionofmyocardial infarction (MI).' However, little isknownabout themechanisms of postinfarction angina occurring atrest. Inthe presence ofsevere stenosis inacoronary artery, very small increases inheart rate orother determinants of myocardial oxygenconsumption, whichcanoccur evenatrest, maybeenough toalter themyocardial oxygensupply-demand relationship.2-4 Schuster and Bullkley5 recently suggested that aninterruption of collateral blood flowcaused byacute occlusion ofa donorartery mayberesponsible forpostinfarction angina. Coronary arterial spasmisanother possible cause ofpostinfarction angina. Oliva andBreckinridge6 indicated that spasmwaspresent intheoccluded artery inasmanyas40%ofpatients withAMI.However, there hasbeennoreport ofpatients inwhomcoronary arterial spasmwasresponsible forpostinfarction angina. Inthis report, wedescribe theclinical features ofsix patients thatstrongly suggest thatpostinfarction angina wasproduced bycoronary arterial spasm. Materials andMethods Sixpatients admitted withAMI toourcoronary careunit(CCU)hadrecurrent ST-segment elevations. Thediagnosis ofAMIwasmadeonthebasis of severe prolonged chest pain andelectrocardiographic findings ofabnormal Q waveswithST-segment elevations. Thediagnosis wasconfirmed byevolutionary ECGchanges andelevations ofserumenzymes.7 There werethree males andthree females, ages43-72years

The role of prostanoids in a swine model of coronary artery spasm was examined. Eighteen miniature pigs underwent endothelial denudation of the left coronary artery (left circumflex branch in 14 pigs and left anterior descending branch in 4 pigs) followed by high cholesterol feeding. Three months after the denudation, when coronary artery spasm was repeatedly provoked along the denuded portion of the coronary artery by histamine, the vasoconstrictive effect of thromboxane A2 and the preventive effects of indomethacin and prostacyclin against histamine-induced coronary artery spasm were examined. Intracoronary administration of thiothromboxane A2, 200 micrograms, a stable thromboxane A2 analog, failed to provoke coronary artery spasm (seven of seven cases) but nonselectively constricted the coronary artery by 33%. Intravenous administration of indomethacin, 2 mg/kg, or continuous intravenous infusion of prostacyclin, 50 ng/kg per min, failed to prevent histamine-induced coronary artery spasm (four of four and eight of eight cases, respectively), yet the spasm was all but prevented by intravenous pretreatment with diphenhydramine at a dose of 1 mg/kg. Thus, in this swine model, prostanoids may not play a primary role in the occurrence of coronary artery spasm.

The effects of glyceryl trinitrate and dipyridamole on induced ischaemia were studied in awake dogs during transient coronary occlusion before and after collateral development. Seventeen dogs were instrumented under sterile conditions with a miniature pressure gauge to measure left ventricular pressure, a cannula for aortic pressure, and pairs of piezoelectric crystals towards the subendocardium of the left ventricle for regional segment length measurements. A hydraulic cuff occluder and Doppler flow probe were placed around the left circumflex coronary artery. Collateral function was increased by repeated 2 min coronary occlusions at 32 min intervals for 2-9 days until regional wall motion returned to preocclusive values, despite the persistence of coronary occlusion. The effects of glyceryl trinitrate and dipyridamole were studied after the initial haemodynamic changes had subsided. Collateral function was quantified by integrating changes in end systolic length of the ischaemic area during coronary occlusion. Before collateral development the end systolic length area was 29.4(2.4) cm X s and was unchanged by glyceryl trinitrate or dipyridamole. After the development of collaterals the end systolic length area decreased from 4.1(1.1) to 2.2(1.0) cm X s (p less than 0.01) after glyceryl trinitrate and increased to 14.9(1.7) cm X s (p less than 0.01) after dipyridamole. Therefore, glyceryl trinitrate acted directly on collaterals and improved the induced ischaemia, whereas dipyridamole exaggerated the regional wall motion abnormality.

Effects of diltiazem, a recently introduced calcium antagonist, on exercise performance were studied in nine coronary disease patients with effort angina. The duration of exercise before the onset of angina and the time to the onset of ischemic ST depression 2 hours after 90 mg of oral diltiazem were compared with those 2 hours after oral placebo and a few minutes after 0.3 mg of sublingual nitroglycerin. Diltiazem prolonged the duration of exercise in all nine patients (average 2.5 minutes, p less than 0.001) and delayed the onset of ischemic ST depression (average 2.4 minutes, p less than 0.001). The increment of the duration of exercise and the time to the onset of ischemic ST depression following 90 mg of oral diltiazem were almost equivalent to that following sublingual nitroglycerin. These results in fixed coronary atherosclerosis indicate the clinical antianginal efficacy of diltiazem which persists for at least 2 hours after oral administration.

A 28-year-old female was discovered to have mitral stenosis associated with ventricular septal defect, patent ductus arteriosus and tubular hypoplasia of the ascending aorta. The diagnosis of such complex anomalies was con firmed by an echocardiographic and cardiac catheterization study. Congenital mitral stenosis is a rare cardiac malformation and usually results in early death. This patient is a relatively long survival case in spite of many complications.

Echocardiographic studies of a 19-year-old female with Ebstein's anomaly and type B Wolff-Parkinson-White syndrome showed an earlier closure of the anterior tricuspid leaflet (ATL) than of the anterior mitral leaflet (AML), contrary to the previous reports. The interval between the closure of the ATL and the AML was 20 msec and 30 msec, respectively, before and after administration of edrophonium chloride. However, closure of the AML preceded that of the ATL after administration of atropine sulfate and during supraventricular tachycardia by 10 msec and 60 msec, respectively, concomitant with the shortening of the duration of the QRS complex. We conclude that early closure of the ATL may depend on preexcitation of the right ventricle.

To examine the vasospastic cause of myocardial infarction (MI) we studied 1) the incidence of rest angina before MI, 2) clinical features of postinfarction angina and 3) the occurrence of MI in variant angina. 1) Of 178 patients with MI, 60 (34%) experienced rest angina for 1 day to 10 years before the onset of MI. The incidence of rest angina was significantly higher in patients having milder coronary stenosis of 75% or less (15/30, 50%) than in others having severe stenosis of 90% or more (45/148, 30%), p less than 0.05. 2) Postinfarction angina with ST elevation was observed in 16 patients (9%) and ST elevation developed in leads with pathological Q waves in all patients. The incidence of postinfarction angina was significantly higher in those having milder coronary stenosis than in others having severe stenosis, (27% versus 5%, p less than 0.005). Patients with postinfarction angina experienced rest angina before MI more frequently (81%) than others (29%, p less than 0.005). Sublingual nitroglycerin was effective in relieving postinfarction angina attacks and oral calcium antagonist prevented attacks in all patients. 3) MI developed in 9 of 97 patients with variant angina. Six patients had transmural and 3, non-transmural MI. Pathological Q waves and/or coronary T waves appeared in leads where ST elevation was observed during anginal attack. In 7 patients MI developed when antispastic agents were not used and in 2, when angina persisted even under treatment with calcium antagonist. These data strongly suggest that the coronary spasm can be a cause of MI in some patients.

Experiments were undertaken to determine if pretreating the animal with coenzyme Q10 (CoQ) protected the cardiac muscle of the isolated heart from the acute toxic injury induced by perfusion with adriamycin. CoQ (15 mg/kg/day) or vehicle alone was injected intraperitoneally into male rats for 7 days. Two hours after the last injection, the hearts were excised and perfused by Langendorff's technique. Perfusion with various concentrations of adriamycin (5, 10, 20, 30 or 50 μg of adriamycin/ml of perfusate) induced a dose-dependent decline in the contractile tension development and a dose-dependent elevation in the resting tension. When adriamycin in perfusate was 10 μg/ml or less than that, the coronary flow rate remained almost constant during the perfusion. No significant recovery in the contractile tension development and the resting tension was obtained by subsequent perfusion without adriamycin. The contractile tension development of the CoQ-pretreated hearts was significantly greater than that of the vehicle-pretreated hearts both during the perfusion with adriamycin (10 μg/ml) for 60 min and during the subsequent adriamycin-free perfusion for 30 min. After 60 min of perfusion with adriamycin, the cardiac stores of ATP, total adenine nucleotide and nicotinamide adenine dinucleotide in the CoQ-pretreated group were significantly higher than those in the vehicle-pretreated group. These results indicate that exogenous CoQ protects the cardiac muscle from the deterioraion in mechanical function induced by adriamycin. Better mechanical function of CoQ-pretreated hearts was attributable to relatively higher ATP stores presumably due to lesser loss of adenine nucleotide pool from the cardiac cells.

Despite a large number of papers concerning coronary spasm, its mechanism still remains unsolved. Several cases have been reported in which coronary spasm was triggered by allergy. Since histamine is one of the causative substances released in allergic reactions, we speculated on some involvement of an allergic mechanism in the pathogenesis of coronary spasm. We retrospectively examined by questionnaire the incidence of allergic history in patients with variant angina (n=47) and compared it with that in patients with non-ischemic heart diseases (n=83). We could not find any relationship between coronary spasm and allergy. Furthermore, we have not experienced any case in which myocardial ischemia was provoked by an allergic reaction. Accordingly, allergy could not be a major cause of coronary spasm in our present experience.

Effects of divalent cations on fibrinogen and its reaction with thrombin were re-examined and correlated to improve definition of mechanisms underlying the acceleration of clot formation by the ions. The rate of release of fibrinopeptides from fibrinogen was not affected by any of the specific ions studied, but increased rates of fibrin monomer polymerization were obtained with all but magnesium ions. Maximal acceleration of monomer polymerization was observed with the divalent ions at concentration of 2.5-5 mM, and no added specific ion effects were observed with much higher levels. The acceleratory ions were found to have a corresponding effect on the solubility of fibrinogen, as judged from acceleration of its precipitation at low temperature. Although magnesium ions had no effect on fibrin monomer polymerization, they did have a low ranking effect on cryoprecipitation. These data confirm that the principal effect of divalent cations in the fibrinogen-fibrin transformation is to accelerate fibrin monomer polymerization, and suggest that the acceleration is associated with effects on the solubility of fibrinogen.

A 12 lead electrocardiogram was recorded during treadmill exercise in 57 patients with variant angina in whom coronary angiography was performed. Thirty six patients performed exercise tests with and without calcium antagonists, and 21 performed them only with calcium antagonists. In 55 patients calcium antagonists had prevented spontaneous attacks of variant angina for more than two days before the test. The other two patients were given a single dose of diltiazem (90 mg) two hours before the test. Exercise testing without calcium antagonists induced ST segment elevation with chest pain in nine patients, ST segment depression in 10 (nine with chest pain), and no important shift of the ST segment in 17. Five patients had severe coronary stenosis (greater than or equal to 75%) and all of them showed positive response. Thirty one patients had no important coronary stenosis and 14 of them showed positive response. The sensitivity of the exercise test in detecting a coronary stenosis greater than or equal to 75% was 100% without calcium antagonists but the specificity was low (55%). When the exercise test was done in patients taking calcium antagonists, only two (specificity 96%) of 48 patients without severe coronary stenosis showed positive response (elevation of ST segment in one and depression in another) whereas all nine patients with severe coronary stenosis had a positive response (depression of ST segment in six and elevation in three (sensitivity 100%). It is concluded that exercise testing with calcium antagonists may be a useful method for detecting severe coronary stenosis in patients with variant angina.

Relationship of coronary perfusion pressure with total and regional myocardial blood flow in right ventricular free wall was studied in 10 anaesthetised open chest dogs. The right coronary artery was perfused by an autoperfusion system from the carotid artery. Total coronary blood flow into the perfused area was measured by an extracorporeal electromagnetic flow probe. Critical perfusion pressure of the right coronary artery, defined as the lowest pressure level below which the regional wall motion deteriorated, was 39(SEM1) mm Hg. Reactive hyperaemia was noted at 60(2) mm Hg, a level well above the critical perfusion pressure. There was an inverse linear relation between the level of reactive hyperaemia and perfusion pressure. Regional myocardial blood flow was measured by a tracer microsphere technique at control condition, just above and below the critical perfusion pressures and during coronary occlusion. This correlated closely with values obtained by an electromagnetic flow probe (r = 0.94, p less than 0.001) and both values were dependent on the level of perfusion pressure. Endocardial to epicardial flow ratio remained at unity at any level of coronary perfusion pressure. Thus the level of coronary perfusion pressure was a major determinant of the regional myocardial blood flow into the right coronary artery, and autoregulation of the regional myocardial blood flow was not apparent across the wall, despite the presence of a reactive hyperaemia.

Effects of adenosine 3',5'-cyclic monophosphate (cAMP) on single Ca-activated K current (IK(Ca)) in cultured smooth muscle cells of the rat aorta were investigated with the patch-clamp technique. In cell-attached patch configurations, extracellular application of isoproterenol (10(-5) M) increased the Ca-activated K currents. The increase in the currents was due to an increase in the probability of channel openings (Po). Neither unit conductance nor the maximum number of the channel in the patch was affected by the drug. The effects were inhibited by adding propranolol (10(-6) M). The extracellular application of forskolin (10(-5) M) or dibutyryl cAMP (10(-4) M) mimicked the effects of isoproterenol. In inside-out patch configurations, activated cAMP-dependent protein kinase (A kinase) in the bathing solution increased the sensitivity of the Ca-activated K channels to intracellular free calcium concentration ([Ca]i) and enhanced Po. Kinetic analyses of the IK(Ca) showed that cAMP-dependent phosphorylation of the Ca-activated K channels significantly reduced the mean closed time between bursting openings. We conclude from these observations that the Ca-activated K channels in aortic cells may increase Po through cAMP-dependent phosphorylation.

Characteristics of the bindings of [3H](-)dihydroalprenolol, [125I](-)iodocyanopindolol, [3H]prazosin, [3H]yohimbine, and [3H]nitrendipine to porcine coronary membranes were investigated and the results compared with studies of porcine aortic membranes. In the equilibrium binding study carried out in sarcolemma-enriched fractions, there were no major differences in the Kd values of these radioligands between coronary artery and aorta. However, the densities of beta-, alpha 1-, and alpha 2-adrenoceptors and [3H]nitrendipine receptors of coronary artery were 258, 12, 12, and 561 fmol/mg protein, respectively, while those of aorta were 37, 525, 1,000, and 215 fmol/mg protein. beta-Adrenergic agonists competed with [3H](-)dihydroalprenolol binding sites in coronary artery, the order of potency being (-)isoproterenol greater than (-)norepinephrine greater than (-)epinephrine greater than (+)isoproterenol. In case of aorta, the order was (-)isoproterenol greater than (-)epinephrine greater than (-)norepinephrine. The competition by (+/-)bisoprolol (beta 1-selective antagonist) and ICI 118,551 (beta 2-selective antagonist) for [125I](-)iodocyanopindolol binding sites in coronary artery resulted in nonlinear Hofstee plots (beta 1:beta 2 = 90%:10%). In case of aorta, linear Hofstee plots were obtained. From these results, we conclude that coronary beta-receptors in pigs are predominantly of beta 1-type, while those of aorta are of beta 2-type; regarding the relative population of adrenoceptors, coronary artery is beta-dominant (beta/alpha = 11), while aorta is alpha-dominant (beta/alpha = 0.02); compared with alpha-adrenoceptors, coronary artery has a greater number of [3H]nitrendipine binding sites (nitrendipine/alpha-adrenoceptor = 23) than aorta (nitrendipine/alpha-adrenoceptor = 0.14).