Masaaki Kakihana

Coronary circulation in dogs with an experimental decrease in aortic compliance

OBJECTIVES This study was designed to investigate the effects of decreased aortic compliance on the coronary circulation. BACKGROUND A decrease in aortic compliance due to arteriosclerosis is observed in patients with coronary artery disease. However, the effects of decreased aortic compliance on the coronary circulation have not yet been investigated sufficiently. METHODS Hemodynamics, subendocardial electrocardiogram (ECG), myocardial segmental length and myocardial blood flow were investigated in six dogs with aortic bandaging (bandaged group) and five dogs with a sham operation (control group) at rest and during pacing 4 weeks after surgery. RESULTS Aortic compliance in the bandaged group was less than that in the control group (0.24 +/- 0.20 vs. 0.50 +/- 0.22 ml/mm Hg, p < 0.05). Pulse pressure and the tension-time index were significantly greater in the bandaged group than in the control group, but systemic vascular resistance was not altered significantly. The subendocardial/subepicardial flow ratio was lower in the bandaged group than in the control group (0.95 +/- 0.31 vs. 1.57 +/- 0.26, p < 0.05). In the region supplied by the left circumflex artery with a stenosis that was adjusted to eliminate reactive hyperemia, rapid atrial pacing (heart rate 200 beats/min) further decreased endocardial flow and the endocardial/epicardial flow ratio in the bandaged group. Moreover, both the reduction of segmental shortening and the ST elevation on the subendocardial ECG in the left circumflex-supplied region during pacing were greater in the bandaged group. CONCLUSIONS These results indicate that decreased aortic compliance greatly increases the risk of subendocardial ischemia in the presence of coronary stenosis.

Chronically decreased aortic distensibility causes deterioration of coronary perfusion during increased left ventricular contraction

OBJECTIVES This study investigated the long-term effects of decreased aortic distensibility on the heart in relation to coronary perfusion. BACKGROUND Aortic distensibility is decreased in patients with atherosclerosis and hypertension and in the elderly. However, the effect of a long-term decrease in aortic distensibility on coronary perfusion has not been fully investigated. METHODS Twelve anesthetized dogs underwent thoracotomy and were allocated to two groups: Group I included six control dogs with a normal aorta; Group II included six dogs with decreased aortic distensibility produced by banding the descending aorta. After 4 to 6 weeks, the dogs had a second operation to measure coronary artery flow and transmural flow distribution. Because the effect of decreased aortic distensibility on coronary perfusion may be affected by ventricular contractility, measurements were performed at baseline and during increased ventricular contraction induced by isoproterenol infusion. RESULTS At baseline, arterial compliance was reduced by 35% in Group II, but there was no change in total mean arterial resistance. Hemodynamic variables, regional wall motion and coronary flow were also similar in both groups. However, during isoproterenol infusion, coronary flow increased more in Group II than in Group I (p < 0.01), and the coronary flow reserve ratio (maximal peak hyperemic flow divided by rest flow) decreased more in Group II than in Group I (mean [+/- SD] 1.9 +/- 0.4 vs. 2.4 +/- 0.3, p < 0.05). Moreover, although the transmural flow distribution was similar in the two groups at baseline, during isoproterenol infusion the endocardial flow increased less in Group II than in Group I (p < 0.05), and the endocardial/epicardial flow ratio was significantly decreased in Group II compared with Group I (mean [+/- SD] 0.70 +/- 0.18 vs. 0.99 +/- 0.22, p < 0.05). The subendocardial electrocardiogram showed ST segment elevation during isoproterenol infusion in Group II (p < 0.05) but not in Group I. CONCLUSIONS These results demonstrate that during increased ventricular contraction, chronically decreased aortic distensibility contributes to a further decrease in the coronary flow reserve ratio, impairs endocardial blood flow and may induce subendocardial ischemia even in the absence of coronary artery stenosis.

Platelet cyclic GMP. A potentially useful indicator to evaluate the effects of nitroglycerin and nitrate tolerance.

BackgroundThe present study was designed to investigate the intracellular production of cyclic GMP (cGMP) in platelets in response to nitroglycerin and to determine the potential clinical value of platelet cGMP as an indicator of the effects of nitroglycerin and nitrate tolerance. Methods and ResultsPlatelet cGMP levels and the diameters of the coronary arteries before and 2 minutes after intracoronary injection of 200 ptg nitroglycerin were measured in 15 patients who had previously received nitrates (nitrates group) and in 16 who had not received any nitrates (no-nitrates group). Platelet cGMP levels increased significantly after nitroglycerin injection in the two groups, but plasma cGMP levels and plasma atrial natriuretic peptide levels did not change. The percent increase in platelet cGMP levels and the percent dilatation of the left anterior descending (LAD) and left circumflex (LCx) coronary arteries after nitroglycerin injection were higher in the no-nitrates group than in the nitrates group (platelet cGMP levels: artery, 74.2±18.3% versus 11.5

Plasma endothelin-1 concentrations in the coronary sinus in dogs with artificially induced myocardial infarction

4.2%, p<.01; vein, 73.6+22.9%o versus 9.0

Effects of enalapril during continuous nitrate therapy: Analysis of diameter of coronary arteries and platelet cyclic guanosine monophosphate

3.1%, p<.01; coronary dilatation: LAD, 46.7

Evaluation of myocardial perfusion abnormality by profile analysis for digital subtraction angiogram.

6.0%o versus 9.9

Decreased aortic compliance aggravates subendocardial ischaemia in dogs with stenosed coronary artery

2.5%, p<.01, LCx, 51.2+8.7% versus 6.1

Aneurysm of patent ductus arteriosus in an adult case: Findings of cardiac catheterization, angiography, and pathology

3.0%o, p<.01). The percent increase in platelet cGMP levels was significantly correlated with the percent dilatation of the coronary arteries (LAD: r=.90, p<.01; LCx: r=.92, p<.01) in the no-nitrates group and not in the nitrates group. ConclusionsThese results indicate that platelet cGMP can be used as an indicator for in situ evaluation of nitroglycerin effects and that patients who have received nitrates develop nitrate tolerance, which affects intracellular production of cGMP and vasodilation in the response to nitroglycerin.

Effects of the rise in aortic pressure on coronary flow reserve in dogs: comparison between constriction of the descending thoracic aorta and injection of methoxamine

We have previously reported the marked increase in plasma levels of endothelin-1 in patients with acute myocardial infarction (AMI). To investigate the effects of severe myocardial ischemia on the production of endothelin-1, plasma concentrations of endothelin-1 were measured by a sandwich-type enzyme immunoassay that we developed recently in both the coronary sinus and the aorta of dogs with artificially induced AMI. Dogs were anesthetized and chests were opened. The proximal left anterior descending coronary artery was completely occluded by ligation for 1 h and then was reperfused for 1 h. Throughout the experiment (at the end of occlusion for 1 h, at the beginning of reperfusion, at the end of reperfusion for 1 h), plasma endothelin-1 levels were not significantly altered either in the coronary sinus or in the aorta. The present findings indicate that severe myocardial ischemia itself does not affect the production of endothelin-1 in the coronary circulation of dogs.

Mitral valve prolapse syndrome with coronary artery spasm: a possible cause of recurrent ventricular tachyarrhythmia.

To investigate the effects of enalapril, an angiotensin-converting enzyme inhibitor, on nitrate tolerance during continuous nitrate therapy, coronary artery diameters and platelet cyclic guanosine monophosphate (cGMP) levels were measured before and 2 minutes after intracoronary injection of nitroglycerin 200 microg in 60 patients with coronary artery disease and were compared among 20 patients treated with nitrates (nitrate group), 20 patients treated with both nitrates and enalapril (enalapril group), and 20 untreated patients (control group). The percent increase in platelet cGMP and coronary dilatation in the nitrate group was significantly less than in the control group, but the percent increase in the enalapril group was significantly greater than that in the nitrate group. These results indicate that enalapril may be helpful as concomitant therapy to maintain the effect of nitrates during continuous nitrate therapy.