Search

The left ventricle's morphological adaptation to high blood pressure is classified into 4 patterns based on mass and wall thickness. The geometric changes caused by maladaptation to pressure overload possibly relate to progression of contractile dysfunction with abnormal energy metabolism. The present study assessed whether the geometric adaptation of the left ventricle (LV) to high blood pressure relates to changes in myocardial energy metabolism, especially free fatty acid (FFA) utilization. Thirty-five patients with essential hypertension underwent echocardiography and dual isotopes myocardial scintigraphy using iodine-123 labeled 15-p-iodophenyl-3-(R,S)-methylpentadecanoic acid (BMIPP, an analogue of a FFA) and thallium-201 (Tl-201). Systolic (endocardial fractional shortening; %FS) and diastolic indices (the ratio of early to atrial filling waves; E/A) of LV function were also assessed. Quantitative myocardial BMIPP uptake was evaluated by the BMIPP/TI-201 myocardial uptake ratio (B/T). The subjects were divided into 4 groups based on LV mass and wall thickness: (1) concentric hypertrophy (CH), (2) eccentric hypertrophy (EH), (3) concentric remodeling (CR), and (4) normal geometry (N). The %FS was lower in the EH group than in the other groups. The mitral E/A ratio in the CH group was lowest. B/T was significantly decreased in the EH group compared with the N group (p < 0.05). B/T correlated with the mitral E/A ratio significantly (p < 0.05, r = 0.42), whereas there was no relationship between %FS and B/T. These results indicate that the geometric changes occurring in hypertensive hearts strongly correlate with alternations in cardiac function and with abnormal myocardial FFA metabolism, and that the latter is associated with diastolic abnormality, but not with systolic function.

The present study seeks to estimate the difference between coronary zero flow pressure (Pzf) by analysis of the baseline pressure-flow relationship and the Pzf calculated during a long diastole in humans. Although Pzf is likely to provide meaningful information about the characteristics of coronary circulation, there are no available data on Pzf in humans because Pzf is overestimated when it is calculated during normal cardiac cycles. Actual Pzf was determined in 15 subjects by analyzing the coronary pressure-flow relationship during a long cardiac cycle induced by an intracoronary adenosine triphosphate (ATP) infusion, and it was compared with the Pzf calculated during a normal cardiac cycle in order to estimate the difference. Pzf calculated during a normal cardiac cycle was 47 +/- 15 mmHg, which decreased to 36 +/- 9mmHg after intracoronary administration of ATP (0.05 mg) whereas actual Pzf was 21 +/- 7 mmHg. Pzf calculated in a pressure-flow relationship during a normal cardiac cycle under vasodilation correlated well with that during a long diastole (r = 0.75, p < 0.01), although it was 15 +/- 6 mmHg greater than the actual Pzf. It was concluded that Pzf during a normal cardiac cycle could be used to anticipate Pzf.

Adenosine triphosphate (ATP) is reported to be released mainly from presynaptic vesicles and cardiomyocytes. The released ATP, which can be degraded to adenosine, may cause coronary vasodilation. However, there is no clear evidence that ATP is degraded to adenosine and causes coronary vasodilation in humans. The present study was undertaken to test whether intracoronary administration of ATP increases myocardial adenosine levels and coronary blood flow. In 11 patients, 3 doses of ATP (0.1, 0.2, and 0.4 mg) were injected into the left anterior descending coronary artery. The velocity of coronary blood flow was measured by Doppler flow probe, and the adenosine concentration in the coronary sinus blood was measured. We also continuously infused ATP (0.2 mg/min) for 1 min in another 10 patients. Coronary blood flow increased dose dependently soon after injection of ATP. Coronary arteriovenous differences in adenosine concentration increased [from 21 +/- 15 to 178 +/- 15 pmol/ml (p < 0.05) 10 sec after the injection of ATP (0.4 mg)] and there were marked reductions in both aortic blood pressure and heart rate. The adenosine levels returned to baseline 20 sec after the injection of ATP, and aortic blood pressure and heart rate also recovered, although coronary blood flow remained increased. Furthermore, continuous infusion of ATP for 1 min increased coronary blood flow velocity and coronary arteriovenous differences in adenosine concentration from 25 +/- 14 to 71 +/- 13 pmol/ml (p < 0.05) in 10 patients. These results indicate that intracoronary administration of ATP immediately increases coronary blood flow and the adenosine concentration of coronary venous blood, which returns to the baseline level thereafter. The differences in the time courses of increases in coronary venous adenosine levels and coronary blood flow after ATP injections suggest that vasodilatory mechanisms other than adenosine, eg, nitric oxide and prostaglandins, may also be involved in the ATP-induced coronary vasodilation. ATP may be used as a cardioprotective agent as well as adenosine.

To elucidate the relationship between lactate metabolism following reperfusion and restoration of left ventricular (LV) function, we assessed serial changes in transcardiac lactate metabolism following reperfusion therapy in 67 patients admitted to hospital within 6 h of the onset of acute anteroseptal myocardial infarction. Left ventriculograms taken about 30 min after reperfusion therapy revealed marked dyskinesis in the anteroapical region in all subjects. According to the regional ejection fraction (rEF), determined 4 weeks later as an index of LV function, patients were divided into 3 group: 1) Restored LV group: 28 patients with reperfusion and restored LV function (rEF greater than 30%); 2) Poor LV group: 26 patients with reperfusion but poor LV function (rEF less than 30%); 3) Failure group: 13 patients with failed reperfusion and occluded left anterior descending coronary artery. Although there was no difference in elapsed time and time to peak creatine phosphokinase (CPK) between the former 2 groups, the Restored LV group demonstrated lower peak CPK values, suggesting that these patients had less myocardial injury. Immediately after reperfusion, both groups showed transcardiac lactate production. In the Restored LV group, aerobic lactate metabolism was restored early after reperfusion (at 6 h), while in the Poor LV group prolonged anaerobic lactate metabolism was observed. These results suggest that an early restoration of aerobic metabolism might be a sign of stunned and viable myocardium, and a sustained lactate production might relate to a sustained process of myocardial injury.

In this study ECG changes were analyzed to assess the acute effects of antegrade blood flow on the ECG in patients with AMI. The study population consisted of 22 patients with MI in whom the totally occluded left anterior descending artery (LAD) or right coronary artery (RCA) was recanalized by intracoronary urokinase infusion (recanalized group) and 14 patients in whom the occluded coronary artery was not successfully recanalized (control group). No significant difference was found in the sum of ST segment elevation (V2-V4 leads for the LAD-occluded group, II, III and aVF leads for the RCA-occluded group) before urokinase infusion. In the recanalized group sigma ST abruptly increased in 5 min after recanalization in 13 of 16 LAD-occluded patients from 1.49 +/- 0.89 mV to 2.44 +/- 1.67 mV (p less than 0.005), and in 4 of 6 RCA-occluded patients from 0.66 +/- 0.12 mV to 1.42 +/- 0.52 mV (p less than 0.01). However increased sigma ST in the recanalized group was reduced to the control value existing before recanalization within 30 min after recanalization and continued to decline more rapidly than in the control group. These transient ST segment elevations were not correlated with long-term angiographic determinants of left ventricular function. We conclude that ST segment shows abrupt augmentation after successful thrombolysis and that continuous ST segment monitoring is useful for assessing thrombolysis in AMI.

To clarify the role of thromboxane A2 (TXA2) in evoking coronary spasm, we compared coronary arterial spasticity induced by ergonovine maleate (EM) with coronary sinus thromboxane B2 (TXB2: a stable catabolite of TXA2) in 34 patients with documented variant angina and 11 patients with chest pain syndrome (CPS). We also examined the effect of OKY-1581 (8 mg/kg, i.v.), a TXA2 synthetase inhibitor, on the coronary arterial spasticity of these patients. When blood samples were taken from coronary sinus just before EM test, all patients with variant angina exhibiting markedly augmented TXB2 levels (424 +/- 138 pg/ml), had positive EM test results, while CPS exhibiting lower TXB2 levels (223 +/- 38 pg/ml), had negative EM test. We found that the amounts of EM needed to induce coronary spasm were inversely correlated with TXB2 levels in coronary sinus. In 7 out of these 8 patients, OKY-1581 was found to attenuate the increased spasticity with reduction of coronary sinus TXB2 levels. In 3 patients, an EM rechallenge at symptomatically quiescent stage resulted in negative test with augmented TXB2 levels being markedly decreased. These findings indicate that increased TXA2 in circulating plasma is closely correlated with the hypersensitivity of coronary arteries to EM in patients with variant angina, suggesting a possible role of augmented TXA2 production in the enhancement of coronary vascular spasticity.

We examined the effects of a new inotrope, OPC-8212 (OPC: 2(1H)-quinolinone), on coronary sinus flow (CSF), myocardial oxygen consumption, myocardial lactate extraction ratio (LER), cardiac index (CI) and pulmonary arterial diastolic pressure (PADP) in eleven patients with prior myocardial infarction. Measurements were taken before (control) and 8 hours after administration of OPC (480 mg, p.o.). A cardiac function curve was obtained in each stage with rapid intravenous administration of 500 ml of saline (loaded state) after baseline measurements. There was a significant increase in the cardiac index and decrease in the pulmonary arterial diastolic pressure in the loaded state after OPC. Thus the ventricular function curve was shifted to the left and showed a steep incline, indicating an increased inotropic state. On the other hand, myocardial oxygen consumption and myocardial lactate extraction ratio were unchanged. Thus we concluded that OPC improved cardiac performance without increasing myocardial oxygen consumption.

The acute effects of intravenous trapidil on hemodynamics, coronary circulation and myocardial metabolism were evaluated in 19 patients (Group I: 10 patients of chest pain syndrome; Group II: 9 patients of coronary heart disease). The heart rate increased (p less than 0.05) and aortic pressure decreased (p less than 0.01) during a 6-min study period. Pulmonary arterial end-diastolic pressure decreased slightly in both groups and cardiac output increased prominently in Group II. Myocardial oxygen consumption did not change significantly 3 and 6 min after trapidil injection. Coronary sinus flow increased slightly (statistically not significant) despite a decrease in aortic pressure, and thus, coronary vascular resistance decreased significantly in both groups. Coronary A-V O2 difference decreased 3 min after trapidil injection and no significant change in the lactate extraction ratio was observed. The diameter of the left main coronary artery increased by about 6% after an administration of trapidil. These results suggest that trapidil has the beneficial effect of coronary vasodilation and it increases cardiac output, despite a decrease in the preload, without a significant increase in myocardial oxygen consumption. The latter may be due to an afterload reduction effect of this drug.

To examine the angiographic features of vasospastic angina associated with ST segment depression, we attempted to analyze the coronary arteriograms of 12 patients who exhibited ST segment depression during the ergonovine provocative test. Right and left coronary arteriograms were obtained successively within a short period when the ergonovine administration revealed ST segment depression. Eight out of 12 patients showed non-total spastic obstructions in one of the major coronary arteries. Among them, a collateral augmentation was found only in one patient. Two cases exhibited the well-developed collateral channels during non-anginal periods and in one case a collateral blood supply was reduced by the spasm occurred in the donating artery. In another one, the collateral circulation did not change during anginal period. Three out of 4 patients who showed total spastic obstructions demonstrated transiently augmented collateral circulation which was supplied by the non-spastic artery. These findings may indicate that ST segment depression during coronary artery spasm could attribute to a subendocardial ischemia caused by an incomplete occlusion of large coronary artery and transient reduction or augmentation of collateral blood flow.

There has been increased interest in the beneficial effects of atrio-ventricular (AV) pacing over ventricular (V) pacing. This study attempted to evaluate the changes in cardiac output and left ventricular filling dynamics when the pacing mode was switched from V pacing to AV pacing. Study population consisted of 26 patients with multiprogrammable AV pacemakers. Cardiac output was determined as a product of echocardiographically determined cross sectional area of the aortic annulus and Doppler-determined velocity integral of left ventricular outflow over systole. Left ventricular peak rapid filling rate (PFR) and peak atrial filling velocity to peak rapid filling velocity ratio (A/R) were determined from measurements at the mitral annulus. Cardiac output showed a significant improvement when the pacing mode was switched from V to AV pacing, and the percent change ranged from 3 to 73% (average 26%). The improvement in cardiac output brought about by AV synchrony was greater in patients with smaller PFR (r = -0.71, p less than 0.01) and larger A/R ratio (r = 0.77, p less than 0.01). On the other hand, PFR was greater with V pacing than with AV pacing. Greater increment of the PFR was produced by the loss of atrial contraction in patients with smaller PFR (r = -0.82, p less than 0.01) and larger A/R ratio (r = 0.76, p less than 0.01). Thus, AV pacing provides a great improvement in left ventricular filling, i.e., cardiac output, which cannot be obtained with V pacing even with the compensatory enhancement of left ventricular rapid filling. These beneficial effects of AV pacing seemed to be greater in patients with impaired left ventricular rapid filling.

Hemodynamic effects of vasodilator agents (molsidomine, nitroglycerin, isosorbide dinitrate or prostaglandin I2) were studied in 53 patients with acute myocardial infarction. In 20 of these patients, effect on cardiac metabolism were also studied. Patients were divided into four groups according to the Forrester subset and hemodynamic effects of these agents were evaluated by the cardiac index (CI)-preload (PAEDP) relationship. In patients of Forrester subset II and IV, vasodilators were capable of producing a considerable reduction in preload without a significant decrease in cardiac output. However, in patients of Forrester subset IV, five of six patients had only a minimal improvement in cardiac performance with vasodilator therapy because of a severe pump failure. In these patients, a combination therapy with dopamine was necessary to maintain the cardiac output. In patients with Forrester subset III, vasodilator therapy decreased cardiac index and preload was also reduced. Thus, for these patients vasodilators could not be indicated but volume infusion may be indicated. In patients with Forrester subset I, although vasodilator therapy decreased cardiac output, coronary sinus flow and myocardial oxygen consumption were also decreased, indicating that the vasodilator therapy is also beneficial for patients even without heart failure because of the protective effect of unloading on ischemic myocardium. Three nitrate agents, i.e., molsidomine, nitroglycerin and isosorbide dinitrate, demonstrated the similar effect on hemodynamics; mean blood pressure and PAEDP decreased by 7-10% and 20-29%, respectively, while systemic vascular resistance was not significantly decreased. In contrast to nitrates, PGI2 decreased mean blood pressure and systemic vascular resistance significantly, whereas a decrease in PAEDP was minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary vasospasms are usually indicated by ST elevation or depression in the electrocardiogram (ECG). To test the hypothesis that ST elevation represents more severe myocardial ischemia than does ST depression, we determined the coronary sinus blood flow (CSBF) and the transcardiac lactate extraction ratio (LER) in 19 selected patients who had focal vasospasms in the left anterior descending artery. In 10 patients, ergonovine (0.11 +/- 0.02 mg, mean +/- SEM) provoked severe (total or subtotal) coronary vasospasm with ST elevation. Under these conditions, CSBF significantly decreased (from 97 +/- 8 ml/min to 79 +/- 5 ml/min, p less than 0.01) with a marked reduction in LER (from 29 +/- 5% to -14 +/- 6%, p less than 0.01). In contrast, 10 vasospastic events with ST depression after ergonovine (0.15 +/- 0.04 mg, NS) were recognized as mild spastic narrowing or severe spasms with well developed collateral circulation. Alteration of CSBF was significant in only a few patients and the overall CSBF response was non-significant (from 106 +/- 12 ml/min to 103 +/- 13 ml/min). The reduction in LER in this group was less pronounced than those in patients with ST elevation (p less than 0.05). These results indicate that coronary vasospasm with ST elevation may be related to the more pronounced reduction in coronary blood flow accompanied by more severe myocardial ischemia. Such observations may support the contention that some ischemic events associated with ST elevation or depression can be interpreted as a continuous spectrum of vasospastic disorders.