Regulation Of Coronary Vascular Resistance Research Articles

L-Arginine-Nitric Oxide-Asymmetric Dimethylarginine Pathway and the Coronary Circulation: Translation of Basic Science Results to Clinical Practice

By 1980, it was thought that we already knew most of the major mechanisms regulating vascular tone. However, after the somewhat serendipity discovery that endothelium is involved in mediation of relaxation to acetylcholine, a whole new world opened up and we had to rewrite our concept regarding vascular function and its regulation (not to mention many other fields). The new player was an endothelium derived relaxing factor, which molecular constitution has been identified to be nitric oxide (NO). This review summarizes the major molecular steps concerning how NO is synthetized from L-arginine. Also, the fate of L-arginine is described via the arginase and methylation pathways; both of them are affecting substantially the level and efficacy of NO. In vitro and in vivo effects of L-arginine are summarized and controversial clinical findings are discussed. On the basis of the use of methylated L-arginines, the vasomotor effects of endothelial NO released to agonists and increases in flow/wall shear stress (a major biological stimulus) is summarized. In this review the role of NO in the regulation of coronary vascular resistance, hence blood flow, is delineated and the somewhat questionable clinical use of NO donors is discussed. We made an attempt to summarize the biosynthesis, role, and molecular mechanisms of endogenously produced methylated L-arginine, asymmetric dimethylarginine (ADMA) in modulating vascular resistance, affecting the function of the heart. Additionally, the relationship between ADMA level and various cardiovascular diseases is described, such as atherosclerosis, coronary artery disease (CAD), ischemia/reperfusion injuries, and different types of coronary revascularization. A novel aspect of coronary vasomotor regulation is identified in which the pericardial fluid ADMA and endothelin play putative roles. Finally, some of the open possibilities for future research on L-arginine-NO-ADMA signaling are highlighted.

‘Cold as ice’, why do old coronary arteries pay the price?

‘Cold as ice’, why do old coronary arteries pay the price?

Nitric oxide‐dependent regulation of coronary vascular resistance in hypertension

Hypertension is associated with impaired endothelium dependent relaxations in many vascular beds. Evidence from the coronary vasculature offers conflicting results. The current investigation examined the role of NO in regulating coronary vascular resistance (CVR) in spontaneously hypertensive rats (SHR) and their normotensive counterparts (WKY). Rats were anesthetized, the hearts were removed and the aorta was cannulated to allow for retrograde coronary perfusion using a constant flow Langendorff set‐up. Flow was assigned based on heart weight which was estimated from body weight. SHR had a greater baseline CVR than the WKY (6.72±0.34 vs 4.97±0.62 mmHg/ml/min, p<0.05). Following ET‐1 administration SHR had a greater resistance (9.82±0.75 vs 6.87±0.96 mmHg/ml/min, p<0.05) although the absolute change was not different. There were no differences in maximal reduction in CVR to bradykinin (BK) or sensitivity to BK. Treatment with LNAME caused an increase in resistance in both groups although the change in resistance was not different between the SHR and WKY (3.46±0.41 vs 3.02±0.69 p>0.05). LNAME completely abolished the BK induced reduction in CVR in both the SHR and WKY; the response to sodium nitroprusside was unchanged. Thus, the response to BK is NO dependent in both SHR and WKY. The CVR is elevated in the SHR and inhibition of eNOS increases CVR to a similar extent in both strains.Funded by NSERC & HSFO

Abstract 2085: Increased Regional Coronary Vascular Resistance During Hyperemia in Hypertrophic Cardiomyopathy Is Associated with Reduced Myocardial Blood Volume

Introduction: In patients with hypertrophic cardiomyopathy ( HCM ), myocardial blood flow ( MBF ) is decreased during hyperemia because of high coronary vascular resistance. Recently myocardial blood volume ( MBV ) can be estimated in vivo using myocardial contrast echocardiography ( MCE ) with the compensation for acoustic field inhomogeneity. The relationship between MBV and coronary resistance, however, has not been investigated. We thus assessed the hypothesis that increased regional coronary vascular resistance during hyperemia in HCM is associated with reduced MBV. Methods: In 13 patients with HCM ( H , 53±16 years) with asymmetric septal hypertrophy and 9 normal volunteers ( N , 54±11 years), MCE was performed under infusion of Levovist at rest and during hyperemia induced by ATP. Apical 4-chamber views of intermittent harmonic power Doppler imaging were acquired at end-diastole of every sixth beat. MBV was calculated as 10 X/10 ×100%, where X was myocardial contrast intensity minus contrast intensity of the adjacent intracavity blood pool in dB. 15 O-water PET was performed to measure regional MBF. These parameters were measured in the interventricular septum ( IVS ) and LV posterolateral ( PL ) wall. Regional coronary vascular resistance was calculated as (mean blood pressure)/MBF. Results: Wall thickness was significantly greater in H than in N (IVS: 19±4 vs 10±1 mm, p<0.0001; PL: 10±1 vs 9±1 mm, p<0.05). MBV of IVS was lower in H than in N (rest: 2.1±0.7 vs 3.5±1.1%, p<0.01; hyperemia: 2.1±1.3 vs 4.3±1.7%, p<0.01), whereas MBV of PL wall did not differ between groups. Coronary resistance at rest did not differ between groups, but the resistance during hyperemia was significantly greater in H than in N (IVS: 59±16 vs 31±14 mmHg·min·g·ml −1 , p<0.001; PL: 40±10 vs 30±11 mmHg·min·g·ml −1 , p<0.05). Coronary resistance at rest did not correlate with MBV, whereas that during hyperemia inversely correlated with MBV during hyperemia (r=−0.77, p<0.0001) as well as MBV at rest (r=−0.65, p<0.0001). Conclusions: Increased coronary vascular resistance during hyperemia in HCM was significantly associated with reduced MBV. MCE is useful for assessing the dynamic function of coronary circulation in the clinical setting.

Instantaneous diastolic pressure–flow relationship in arterial coronary bypass grafts

The objective of this study was to describe the diastolic pressure-flow relationship and to assess critical occlusion pressure in arterial coronary bypass grafts in human beings. Fifteen patients were studied following elective surgical coronary artery bypass grafting. Flow in the left internal mammary artery bypass to the left anterior descending artery was measured and simultaneously, aortic pressure, coronary sinus pressure and left ventricular end-diastolic pressure were recorded. The zero-flow pressure intercept as a measure of critical occlusion pressure was extrapolated from the linear regression analysis of the instantaneous diastolic pressure-flow relationship. Mean diastolic flow was 46 +/- 17 mL min(-1), mean diastolic aortic pressure was 60.5 +/- 10.0 mmHg. Diastolic blood flow was linearly related to the respective aortic pressure in all patients (R-values 0.7-0.99). The regression lines had a mean slope of 2.1 +/- 1.2 mL min(-1) mmHg(-1). Mean critical occlusion pressure was 32.3 +/- 9.9 mmHg and exceeded mean coronary sinus pressure and mean left ventricular end-diastolic pressure by factors of 3.1 and 2.6, respectively. Our data demonstrate the presence of a vascular waterfall phenomenon in the coronary circulation after internal mammary artery bypass grafting. Critical occlusion pressure in arterial grafts considerably exceeds coronary sinus pressure as well as left ventricular end-diastolic pressure and should thus be used as the effective downstream pressure when calculating coronary perfusion pressure. Our data further suggest that the slope of diastolic pressure-flow relationships provides a more rational approach to assess regional coronary vascular resistance than conventional calculations of coronary vascular resistance.

Heterogeneity of coronary vasomotion.

Apart from local heterogeneities of myocardial blood flow, the regulation of vascular tone is equally complex. Changes in vascular tone are essential for the adaptation of coronary blood flow to varying metabolic demands. The majority of coronary vascular resistance is found in the microcirculation, that is, in vessels with less than 150-200 microns in diameter; therefore, understanding the regulatory mechanisms that exercise control of the tone of these vessels is paramount to our understanding the control of myocardial perfusion. Recently, it became evident that different regulatory systems such as metabolic, neurohumoral, myogenic, and flow-mediated mechanisms have preferential effects on particular microvascular segments. However, the significance of specific vasoactive mediators is still under investigation. Growth factors, which are synthesized in cells in the surrounding of vessels such as mast cells and cardiac myocytes, have recently been suggested to play a role in the coordination of endothelium-dependent and endothelium-independent vasoactive mechanisms. The aim of this review is, first, to focus on the heterogeneity of the regulation of coronary vascular resistance in general and, second, to discuss recent studies showing a possible role of growth factors, especially fibroblast growth factor (FGF), heparin, and endothelin, as modulators of microvascular tone.

Neural regulation of coronary vascular resistance: role of nitric oxide in reflex cholinergic coronary vasodilation in normal and pathophysiologic states.

A number of reflexes participate in the control of coronary vascular resistance through activation of the sympathetic or parasympathetic nervous system. Classically, activation of vagal efferent fibers to the heart results in vasodilation due to the release of acetylcholine and activation of muscarinic receptors. Recently, we have found that activation of a number of reflexes in conscious dogs, the Bezold-Jarisch reflex and the carotid chemoreflex in particular, results in cholinergic coronary vasodilation which is blocked by an inhibitor of nitric oxide synthesis, nitro-L-arginine. After the development of pacing-induced heart failure, the cholinergic dilation subsequent to activation of the Bezold-Jarisch or carotid chemoreflex is essentially abolished, since coronary blood vessels no longer produce nitric oxide. In contrast, after brief exercise training, there is a potentiation of Bezold-Jarisch reflex-induced coronary vasodilation since exercise upregulates nitric oxide production by coronary blood vessels. Since the Bezold-Jarisch reflex may be important as a compensatory mechanism during acute myocardial infarction, and the carotid chemoreflex is the acute mechanisms responsible for ameliorating systemic hypoxemia, the role of nitric oxide in reflex cholinergic coronary vasodilation may be essential in the compensatory vascular adjustments evoked by these and other reflexes.

Effects of dexmedetomidine on coronary hemodynamics and myocardial oxygen balance

alpha 2-adrenergic agonists decrease central sympathetic outflow and maintain normal transmural myocardial blood flow distribution, but intravenous bolus doses of these agents can also induce excessive coronary vasoconstriction and myocardial ischemia. The hypothesis of the present study was that a rapid intravenous bolus of dexmedetomidine, a specific alpha 2-adrenergic agonist, will cause coronary vasoconstriction and accompanying myocardial ischemia in young pigs. Prospective, controlled study on experimental animals. Animal laboratory of a university cardiorespiratory research center. Twelve domestic 8-week-old open-chest pigs, anesthetized with high-dose fentanyl. Another six pigs served as controls. Sequential intravenous dexmedetomidine boluses of 3, 10, and 30 mg/kg were administered, and responses were measured during peak changes (2 minutes after injection) and during recovery after each dose. Left anterior descending coronary artery blood flow, calculated regional coronary vascular resistance, myocardial extraction of oxygen and lactate, plasma catecholamine levels, and conventional central hemodynamic parameters were measured. The two higher doses of dexmedetomidine induced 21% and 29% immediate increases in left anterior descending coronary artery blood flow. At the same time mean systemic blood pressure and pulmonary capillary wedge pressure increased, and calculated regional coronary vascular resistance increased. Myocardial extraction of oxygen and lactate remained unchanged. Large intravenous doses of dexmedetomidine caused moderate regional coronary vasoconstriction without metabolic signs of myocardial ischemia in young domestic pigs at the same time as a marked vasoconstrictive response in the systemic circulation.

Regulation of coronary blood flow: coordination of heterogeneous control mechanisms in vascular microdomains

The technology is available for the study of the coronary microcirculation in vivo and in vitro. Coronary microvascular resistance depends continually upon intrinsic and extrinsic regulatory influences operating on different vascular microdomains. These regulatory influences are (1) a predominant metabolic influence of multifactorial aetiology (this mechanism is poorly understood); (2) myogenic responsiveness to pressure; (3) endothelium dependent dilatation in response to flow and agonists; and (4) neurohumoral factors. The diameter of a microvessel, and thus the resistance it poses to flow, depends upon local interactions between regulatory mechanisms and also on distant interactions mediated by the effects of transmitted flow and pressure. Distant interactions occur mainly because of a strong capacity for autoregulatory adjustments in the diameter of microvessels of less than 100 μm in diameter. The coronary circulation matches blood flow with oxygen demands by coordinating the resistances within various vascular microdomains, each governed by distinct regulatory mechanisms. Such integration appears advantageous, because the system does not rely on a single mechanism for control. Functional abnormalities of the coronary microcirculation are recognised in disease states including hypercholesterolaemia, atherosclerosis, hypertension, and heart failure. Endothelial dysfunction, marked by reduced release of EDRF, has been described in each of these conditions. The overall consequence of coronary vascular pathology seems likely to be inadequate matching of oxygen and nutrient supply to changing myocardial metabolic demand. One possible reason for the pathophysiological sequelae associated with ischaemic heart disease may be a loss of regulatory mechanisms involved in coronary vasomotor adjustments. As stated above, it appears advantageous to have multiple control mechanisms involved in the regulation of coronary vascular resistance, but if a pathological process renders a mechanism dysfunctional, there is a reduction in “regulatory mechanism reserve.” The potential consequence would be that fewer mechanisms could be recruited for an adjustment of coronary vasomotor tone during physiological and pathophysiological stresses. Perhaps a loss of vasoactive compensatory mechanisms accounts in part for the vulnerability of the coronary circulation in disease states. Finally, we are compelled to emphasise that adjustments in microvascular tone have a significant impact on vasodilator reserve of coronary resistance vessels. It appears that interventions that normally reduce coronary blood flow and oxygen delivery (reductions in perfusion pressure, for example, coronary stenosis; vasoconstrictors, for example, α adrenergic agonists, NO synthase inhibitors) are compensated for by “vasodilator escape” of coronary arterioles. The consequence of this compensatory mechanism is a reduction in the remaining vasodilator reserve, that is, blunting of the remaining mechanisms. Perhaps also this contributes to the augmented effects of constrictors in patients with ischaemic heart disease.

Role of endothelium-derived relaxing factor on coronary blood flow regulation in the dog

The endothelium plays a key role in the regulation of vasoreactivity. To assess its importance on coronary flow regulation, we studied the participation of endothelium-derived relaxing factor-nitric oxide (EDRF-NO) on coronary reactive hyperemia and on the hyperemia that occurs secondary to an increase in myocardial oxygen consumption. In 15 dogs, the reactive hyperemic response decreased substantially after inhibition of EDRF-NO synthesis with N-ω-nitro-L-arginine (P<0.01). In contrast, the hyperemia secondary to an increase in myocardial oxygen consumption, characterized by a linear correlation between myocardial oxygen consumption and coronary flow, did not change significantly after inhibition of EDRF-NO production (regression analysis, P>0.1). Thus EDRF-NO synthesis by the endothelium is an important mechanism mediating the reactive hyperemic response but it does not seem to be essential for the metabolic regulation of coronary vascular resistance during hyperemia induced by an increased metabolic demand on the myocardium.

Effects of dexmedetomidine on systemic and coronary hemodynamics in the anesthetized dog

In addition to central effects, which are the basis of their use in anesthesiology, α 2-adrenergic agonists have direct peripheral cardiovascular effects. Dexmedetomidine (DM) has been found to depress cardiac function in dogs, even after autonomic denervation. The present experiments evaluated the effects of DM on coronary flow, myocardial oxygen extraction, and cardiac function in intact, open chest dogs under enflurane anesthesia. Heart rate (HR), mean arterial pressure (MAP), left ventricular end-diastolic pressure (LVEDP), the first derivative of systolic left ventricular pressure (dP/dt max), and flow in the left anterior descending coronary artery (CBF) were measured and continuously recorded. Cardiac output (CO), plasma catecholamines (CA), hemoglobin and oxygen saturation in arterial, mixed venous, and coronary sinus blood were measured at intervals. Cardiac index (CI), systemic vascular resistance index (SVRI), regional coronary vascular resistance (CVR), and oxygen concentration differences across the systemic [C(a-v̄)O 2], and coronary [C(acs)O 2) circulations were calculated. DM doses of 0.25, 0.5, 1.0, 2.0, and 4.0 μg/kg were given IV at 20-minute intervals. Measurements and samples were taken at peak drug effects and just prior to the next dose. The α 2-antagonist atipamezole, 0.5 mg/kg, was given after the last dose of DM. DM caused immediate dose-dependent increases in SVRI, CVR, LVEDP, C(a-v̄)O 2, and C(a-cs)O 2, and decreases in HR, and Cl, with recovery between doses. DP/dt max declined after the first two doses and stabilized thereafter, as plasma CA fell to minimal levels. Atipamezole completely reversed all changes. The decreases in dP/dt max and CA from initial doses of DM are attributed to a decrease in sympathetic outflow from the CNS, whereas the continuing decline in Cl, coupled with increased LVEDP without further decline in systolic contractility, may have reflected diastolic dysfunction.

Regional myocardial blood flow and left ventricular diastolic properties in pacing-induced ischemia

The relation between left ventricular diastolic abnormalities and myocardial blood flow during ischemia was studied in eight open chest dogs with critical stenoses of the proximal left anterior descending and circumflex coronary arteries. The heart was paced at 1.7 times the heart rate at rest for 3 min. In dogs with coronary stenoses, left ventricular end-diastolic pressure increased from 8 +/- 1 to 14 +/- 2 mm Hg during pacing tachycardia (p less than 0.01) and 16 +/- 3 mm Hg (p less than 0.01) after pacing, with increased end-diastolic and end-systolic segment lengths in the ischemic regions. Left ventricular diastolic pressure-segment length relations for ischemic regions shifted upward during and after pacing tachycardia in dogs with coronary stenoses, indicating decreased regional diastolic distensibility. In dogs without coronary stenoses, the left ventricular diastolic pressure-segment length relation was unaltered. Pacing tachycardia without coronary stenoses induced an increase in anterograde coronary blood flow (assessed by flow meter) in both the left anterior descending and circumflex coronary arteries, and a decrease in regional vascular resistance. In dogs with coronary stenoses, regional vascular resistance before pacing was decreased by 18%; myocardial blood flow (assessed by microspheres) was unchanged in both the left anterior descending and circumflex coronary artery territories. During pacing tachycardia with coronary stenoses, regional coronary vascular resistance did not decrease further; subendocardial myocardial blood flow distal to the left anterior descending coronary artery stenosis decreased (from 1.03 +/- 0.07 to 0.67 +/- 0.12 ml/min per g, p less than 0.01), as did subendocardial to subepicardial blood flow ratio (from 1.04 +/- 0.09 to 0.42 +/- 0.08, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of endothelin on total and regional coronary resistence and on myocardial contractility

Endothelin is a 21-amino acid peptide produced by the endothelium and has a potent vasoconstrictor effect. Because of the importance of the endothelium on vasomotor regulation, we studied the effect of endothelin on total and regional coronary vascular resistance and on myocardial contractility in the intact heart of anesthetized dogs. Intracoronary administration of 2 to 80 pmol/kg of endothelin produced a dose-dependent increase in coronary resistance, ischaemic decrease in myocardial contractility and atrium-ventricular blockade. The increase in resistance was greater towards the outer layer of the left ventricular wall. When the coronaries were perfused at a constant rate and vasoconstriction was prevented with adenosine or nitroglycerine, endothelin did not produce inotropic changes. These results show that endothelin is a potent vasoconstrictor of the resistance coronary vessels, producing a redistribution of transmural blood flow and a decrease in myocardial contractility secondary to ischaemia.

Alterations in endocardial vascular resistance after reperfusion in a low flow, high demand model of ischemia: effects of dipyridamole and WEB-2086, a platelet-activating factor antagonist

To determine if alterations in regional coronary vascular resistance could occur in the type of myocardial ischemia present in severe angina pectoris, regional perfusion and function were studied in 35 conscious sedated dogs. A stenosis producing severe hypokinesia of the perfused segment was created for 2 h on the left anterior descending coronary artery and 10 episodes of 1 min of high demand ischemia (atrial pacing at a rate sufficient to induce dyskinesia in the hypoperfused segment) were superimposed before reperfusion.The dogs were randomized into three treatment groups: control (n=13), dipyridamole (n=10) or WEB-2086 (n=12), an antagonist of the effects of the endogenous platelet-activating factor. During stenosis, residual endocardial blood flow in the ischemic but nonnecrotic area averaged 0.72 ± 0.14, 0.38 ± 0.13 and 0.68 ± 0.17 ml/min per g in the control, WEB-2086 and dipyridamole groups, respectively. Twenty-four hours after reperfusion, endocardial blood flow in the ischemic area was significantly lower in control dogs (1.04 ± 0.15 ml/min per g) than in dogs treated with WEB-2086 (1.44 ± 0.28 ml/min per g; p < 0.03) or dipyridamole (3.00 ± 0.83 ml/min per g; p < 0.01).Accordingly, in control dogs, endocardial coronary vascular resistance in the ischemic area was increased after reperfusion from 85 ± 11 to 124 ± 27 mm Hg/(ml/min per g) (p < 0.05) after 24 h. In contrast, coronary vascular resistance in the ischemic ana remained unchanged in dogs receiving WEB-2086 (77 ± 8 to 79 ± 9 mm Hg/(ml/min per g); p = NS) and it decreased significantly in dogs receiving dipyridamole (72 ± 8 to 44 ± 8 mm Hg/(ml/min per g); p < 0.01). Regional function after 24 h remained depressed in all three groups.These data indicate that low flow, high demand ischemia induces alterations in the subendocardial microvasculature. Such alterations in regional coronary vascular resistance might play a role in several forms of ischemic heart disease such as in severe angina, bat they appear susceptible to improvement by therapeutic interventions that influence granulocyte and platelet activation.

研究会 第23回 河口湖心臓討論会 虚血性心筋障害 心筋虚血における冠血管抵抗の調節部位

研究会 第23回 河口湖心臓討論会 虚血性心筋障害 心筋虚血における冠血管抵抗の調節部位

Neuropeptide Y (NPY): a coronary vasoconstrictor and potentiator of catecholamine-induces coronary constriction

The vasoactive effect of neuropeptideYY (NPY) a peptide commonly found in perivascular nerves, including those of the heart, was assessed in the coronary circulation of the isolated perfused dog heart and in superfused segments of isolated canine coronary arteries. The intracoronary administration of 0.7–23.5 nmol NPY to hearts during beta adrenergic blockade produced a dose-dependent increase in coronary vascular resistance ranging from 0.10 to 0.49 mmHg · min −1 · ml − · 100 g − without changes in myocardial oxygen consumption. The potency of NPY as a coronary vasoconstrictor was about 250 times that of noradrenaline. Pretreating the coronory system of these hearts with NPY caused a marked potentiation of the vasocontractile effect of noradrenaline, displacing its dose-response curve to the left in a non-parallel fashion. The addition of 0.2–3.7 nmol NPY did not induce contraction in superfused helical segments of large coronary arteries but it potentiated the tension developed in response to 0.18 μM adrenaline in a concentration-dependent manner. Pretreatment of these arteries with 3.7 nmol NPY caused a significant leftward displacement of the adrenaline contractile effect. These results show that NPY is a potent coronary vasoconstrictor and a potentiator of the contractile effect of catecholamines and support the hypothesis that NPY may participate in the regulation of coronary vascular resistance.

Nitric oxide release from the isolated guinea pig heart

Nitric oxide (NO) release from isolated guinea pig hearts into the coronary effluent perfusate was measured with a specific spectrophotometric assay. Nitric oxide was continuously released under basal conditions at a rate of 216 ± 36 pmol/min. Bradykinin (5 × 10 −10−10 −8 M) stimulated the release of nitric oxide in a dose-dependent manner. The start of NO release preceded coronary vasodilation by 5 ± 1 s. Our results suggest that the endogenous formation of nitric oxide is quantitatively sufficient to influence the coronary vascular tone and thus may play a significant role in the regulation of coronary vascular resistance.

Global and Regional Myocardial Blood Flow and Metabolism during Equipotent Halothane and Isoflurane Anesthesia in Patients with Coronary Artery Disease

Global and regional myocardial blood flow and metabolism were examined in 20 patients with coronary artery disease before surgical stimulation. Half were anesthetized with halothane (0.8%) and half with isoflurane (1.2%). Coronary perfusion pressure decreased similarly in both groups. During halothane anesthesia coronary sinus blood flow, an index of global perfusion, decreased from an awake value of 129 +/- 7 to 97 +/- 7 ml/min (P less than 0.05), and great cardiac vein blood flow, an index of regional perfusion, decreased from 60 +/- 8 to 44 +/- 5 ml/min (P less than 0.05). In contrast, during isoflurane anesthesia global coronary blood flow increased from 131 +/- 13 to 153 +/- 16 ml/min (P less than 0.05), while regional blood flow decreased from 68 +/- 7 to 56 +/- 6 ml/min (P less than 0.05). Thus, the ratio of great cardiac vein blood flow to coronary sinus blood flow was unchanged during halothane anesthesia but decreased significantly during isoflurane. Neither global nor regional coronary vascular resistance was altered by halothane, whereas isoflurane decreased global coronary vascular resistance without affecting regional coronary vascular resistance. All patients receiving halothane had net myocardial lactate extraction. In the isoflurane group, four patients showed global lactate production and three regional lactate production. All patients demonstrating lactate production also developed electrocardiographic evidence of myocardial ischemia, which was not present before induction. The authors conclude that halothane is a preferable anesthetic to isoflurane in patients with coronary artery disease because the latter has the propensity to induce maldistribution of the coronary circulation and myocardial ischemia.

Electrical stimulation in perifornical lateral hypothalamus decreases coronary blood flow in cats.

Based on evidence implicating the central nervous system in the regulation of coronary vascular resistance and the knowledge that the hypothalamus is a central site for integration of cardiovascular control, studies were undertaken to determine if electrical stimulation in the hypothalamus produced coronary vasoconstriction. In anesthetized cats, following beta-adrenergic receptor blockade, stimulation in perifornical lateral hypothalamus produced a transient decrease in coronary blood flow velocity (30 +/- 5%), a small pressor effect (7 +/- 2 mmHg), and an initial decrease in hindquarter blood flow velocity (51 +/- 5%). The decrease in coronary flow velocity, which had an onset latency of 1-3 s and a duration of 5-15 s, was abolished by ipsilateral stellate ganglionectomy and by intravenous and intracoronary prazosin. The coronary vasoconstriction produced by hypothalamic stimulation was not different from that produced by cardioaccelerator nerve stimulation. These results suggest that electrical stimulation of a hypothalamic site produces an alpha-adrenergic receptor-mediated decrease in coronary blood flow that is unmasked by beta-adrenergic receptor blockade, requires the integrity of ipsilateral cardiac sympathetic innervation, and mimics the coronary response to cardioaccelerator nerve stimulation.

Vasodilating β-adrenoceptor blocking drugs do not redistribute myocardial flow during acute coronary ligation in dogs

The effects of two nonselective β-adrenoceptor blocking drugs, additionally endowed with vasodilating properties with different mechanisms: labetalol which blocks α-adrenoceptors, and bucindolol which nonspecifically relaxes vascular smooth muscle, were investigated on regional myocardial blood flow (RMBF) distribution in ischemic and nonischemic areas and on ST-segment elevation in ischemic areas during intermittent coronary artery occlusion in dogs. Both labetalol and bucindolol reduced heart rate, arterial blood pressure and myocardial oxygen consumption. However, they did not affect coronary vascular resistance and did not induce any favorable coronary blood flow redistribution phenomenon either from the epicardium to the endocardium or from the nonischemic to the ischemic areas. These results indicate that the inability of labetalol and bucindolol to favorably redistribute RMBF was due to the fact that their vasodilating properties counteract one major determinant of RMBF redistribution. i.e. the β-adrenoceptor blockade-induced increase in regional coronary vascular resistance. Finally, both labetalol and bucindolol dose dependently decreased ST-segment elevation in ischemic myocardial areas.