Diastolic Coronary Vascular Resistance Research Articles

Effects of a calcium-channel antagonist on large and small coronary arteries in conscious dogs.

The effects of i.v. nifedipine, 20 micrograms/kg, on left ventricular (LV) pressure, dP/dt, aortic pressure, heart rate, LV diameters, cardiac output, coronary blood flow and left circumflex coronary arterial diameter, and calculations of late diastolic coronary and total peripheral resistances and left circumflex coronary cross-sectional area were examined in 11 conscious dogs. In dogs with spontaneous rhythm, nifedipine induced an early, transient response characterized by hypotension and peak increases in coronary blood flow and decreases in total peripheral and late diastolic coronary vascular resistances. The peak effects on large coronary arteries were observed 2--5 minutes later, when mean arterial pressure was only 8.2 +/- 1.6 mm Hg below control and LV end-diastolic pressure and diameter were not significantly different from control. LV dP/dt was elevated by 7.1 +/- 1.1%, heart rate was elevated by 25 +/- 3.3 beats/min, and cardiac output remained elevated by 54 +/- 7.4%. At this time, coronary cross-sectional area was elevated by 26 +/- 3.0%, late diastolic coronary vascular resistance was reduced by 50 +/- 2.7%, and total peripheral resistance was 40 +/- 3.8% below control. The coronary sinus oxygen content was elevated by 3.4 +/- 0.8 vol% and the arteriovenous oxygen difference fell by 3.5 +/- 0.8 vol%. After beta-adrenergic blockade with propranolol and with heart rate constant or varying, the increases in coronary cross-sectional area and decreases in late diastolic coronary vascular resistance induced by nifedipine were still observed, but were significantly smaller (p less than 0.01). Thus, nifedipine dilates both large coronary arteries and coronary resistance vessels, effects that could be attributed in part to beta-adrenergic mechanisms. Nifedipine also exerts potent effects on coronary and peripheral arterial vessels, but has little effect on preload.

Mechanisms mediating the coronary vascular response to behavioral stress in the dog.

Left circumflex coronary blood flow (CBF) was measured in eight mongrel dogs with 8 MHz continuous wave Doppler flow transducers during classical aversive conditioning. The cardiovascular condition response consisted of significant (P less than 0.01) increases in: (1) mean aortic pressure (16.1%), (2) d(left ventricular pressure)/dt (64.2%), and (3) heart rate (63.2%). The coronary vascular response to behavioral stress consisted of an initial late diastolic decrease in CBF (12.5%) between 5 and 10 seconds after conditional stimulus onset, followed by a significant increase in CBF (96.8%). Concurrently, late diastolic coronary vascular resistance (CVR) first significantly increased (21.9%), then significantly decreased (39.8%). The increase in CVR was attenuated by cardiac pacing and converted into a significant decrease after alpha-receptor blockade. The decrease in CVR was reduced either by cardiac pacing or cardioselective beta-receptor blockage and eliminated by the combination of alpha- and beta-receptor blockade. Thus, these data indicate that the coronary vascular response to stress consisted of two components: an initial alpha-adrenergic coronary vasoconstriction, followed by a more complex vasodilation which was probably mediated by metabolites released secondarily to increases in heart rate and inotropic state.

Coronary vascular resistance during hypocapnia in the closed-chest dog.

AbstractCoronary vascular resistance during whole-body hypocapnia was studied in anesthetized dogs in which coronary blood flow (CBF) was monitored from a catheter-tip flow meter. Intravascular placement of this flow meter did not require opening the chest and avoided possible coronary denervation. Rapid flow meter response permitted determination of coronary vascular resistance during late diastole when vascular compression during systole does not affect the calculation. With rate and depth of ventilation held constant, hypocapnia was induced by a rapid change of the ventilating gas from 95% O2-5% CO2 to 100% O2. Within 30 sec of the change to 100% O2 and prior to any change in mean arterial blood pressure (AP), late diastolic coronary vascular resistance (LDR) decreased from 2.04 ± 0.26 to 1.44 ± 0.20 mm Hg/ml/min. LDR remained below control throughout the hypocapnic period while AP decreased from 122 ± 7 to 111 ± 7 mm Hg and CBF was unchanged. β-Adrenergic blockade with propranolol eliminated the decre...

Classic aversive conditioning of coronary blood flow in mongrel dogs.

Left circumflex coronary blood flow (CBF) was measured in eight dogs during classic aversive conditioning (30-second tone followed by a one-second shock) using continuous-wave Doppler flow transducers. The systemic cardiovascular conditional response consisted of increases in: a) mean aortic pressure of 16.0 ± 4.2 mm Hg (16.1% ↑); b) d(left ventricular pressure)/dt of 1,752 ± 345 mm Hg/sec (64.2% ↑); and c) heart rate of 54 ± 12.3 bpm (63.2% ↑). Late diastolic CBF decreased by 4.0 ± 3.0 ml/min (12.5% ↓) between 5 and 10 seconds after onset of the conditional stimulus and then subsequently increased by 32.0 ± 8.9 ml/min (96.8% ↑). Concurrently, late diastolic coronary vascular resistance first increased by 0.59 ± 0.42 mm Hg/ml/min (21.9% ↑) and then decreased by 1.05 ± 0.22 mm Hg/ml/min (39.8% ↓). All changed values were significantly different from pretrial levels except the initial CBF decrease. This report presents the first detailed description of a coronary vascular conditional response.

Renin-angiotensin system inhibition in conscious sodium-depleted dogs. Effects on systemic and coronary hemodynamics.

The role of the renin-angiotensin system in the regulation of the systemic and coronary circulations during sodium depletion was studied in conscious normotensive dogs by i.v. administration of teprotide (0.5 mg/kg), an angiotensin-converting enzyme inhibitor, and saralasin (0.05-5 mug/kg per min), an angiotensin-receptor antagonist. Sodium depletion was produced by administering a low sodium diet and furosemide for 5 days. Administration of both teprotide and saralasin lowered systemic arterial blood pressure and total peripheral vascular resistance. Simultaneously, cardiac output increased, but left ventricular end-diastolic pressure, dP/dt, and dP/dt/P did not change significantly. Furthermore, both agents reduced diastolic coronary vascular resistance and increased coronary blood flow, but did not affect myocardial oxygen consumption, left ventricular work, or myocardial efficiency. These systemic and coronary vasodilator effects of teprotide and saralasin, however, were not observed in normal dogs on a regular sodium diet; in this group, the only effect noted was a slight increase in arterial pressure during saralasin infusion. Arterial plasma concentration of norepinephrine did not differ between normal and sodiumdepleted dogs, nor did it change significantly after teprotide administration. These results suggest that, during salt depletion, angiotensin II exerts an active vasoconstrictor action on the systemic and coronary vessels, but has no significant effects on myocardial contractility or energetics. It also appears likely that the increase in cardiac output observed in sodiumdepleted dogs after angiotensin inhibition was caused, at least in part, by the decrease in systemic arterial pressure.

Coronary vascular resistance during halothane anesthesia.

To study the effect of halothane on the coronary circulation, the circumflex diastolic coronary vascular resistance was measured in the working heart and total mean coronary resistance (TCR) in the isolated nonworking heart of the dog during administration of 100 per cent oxygen and during administration of 2--3 per cent halothane in oxygen. In the working heart, when the diastolic aortic pressure was kept at a nearly control level, halothane induced decreases of 12 per cent in circumflex diastolic coronary vascular resistance and 18 per cent in left ventricular arteriovenous oxygen content difference and no significant change in diastolic coronary blood flow. This effect occurred in spite of the absence of any significant change of myocardial oxygen consumption. In the nonworking beating, arrested or fibrillating heart, halothane induced a decrease of 24 per cent in total mean coronary resistance. Since the decrease in circumflex diastolic coronary vascular resistance in the working heart connot be attributed to myocardial hypoxia and since the results in the isolated nonworking heart eliminate the influences of mechanical and neurohumoral factors on coronary resistance, it is concluded that the observed decrease in resistance is probably due to vasodilation produced by a direct action of halothane on the coronary vessels. This effect was not modified by beta-adrenergic blockade.

Physiologic Evaluation of Angina Pectoris

Electrocardiographic and ballistocardiographic observations have been the only objective methods easily available for assessment of the state of the coronary circulation. As has been pointed out, however, these methods give only indirect information concerning the hemodynamic status and functional adequacy of the coronary circulation. The extensive pathologic studies of the coronary arteries in angina pectoris”2 have demonstrated that these vessels seldom show a single vascular disturbance, but more often, demonstrate diffuse involvement of the entire coronary vascular tree leading to increased large vessel resistance to blood flow. Physiological principles have been applied to the understanding of other cardiac problems, particularly valvular, congenital and constrictive heart disease and congestive heart failure. They have led to the development of objective hemodynamic methods of evaluation which would appear to be of value for the coronary circulation as well. We have attempted such an approach. Our findings are based on a correlative clinical, electrocardiographic and cardiac catheterization study of 43 patients. Coronary sinus catheterization was performed and coronary blood flow measured by the nitrous oxide technique’ as modified by Goodale and Hackel.4 Diastolic coronary vascular resistance was calculated.5 The group of 43 patients was subdivided as follows: Group 1 was the normal group, composed of 10 patients with negative histories, physical examinations and resting and post-exercise electrocardiograms. Group 2 was the abnormal group, composed of 23 patIents with typical angina pectoris and positive electrocardiographic examinations. Group 3 was designated the unknown group, composed of 10 patients, all of whom complained of atypical chest pain, and In whom the resting and exercise electrocardiograms were negative or equivocal. Three of these patients had left ventricular hypertrophy secondary to aortlc valve disease. The open columns in Figure 1 summarize the results of resting studies performed in normals, in patients with coronary artery disease and in those with increased left ventricular work. Coronary flow was essentially the same in all three groups; in the coronary group it was actually 19 per cent above normal. Diastolic coronary vascular resistance, which encompasses coronary inflow time as well as perfusion pressure, is perhaps the most useful index of the cross-sectional area of the coronary vascular bed. Again, no difference was found among these groups. In a recent report evaluating internal mammary ligation for angina pectoris, nitrous oxide flows were performed at rest. The authors found no difference in values before and after ligation, and therefore, concluded