Hai Bin Dai

Blood and albumin cardioplegia preserve endothelium-dependent microvascular responses

Alterations of vascular reactivity may be a cause of reduced myocardial perfusion after cardioplegic arrest. The effects of blood and albumin cardioplegia on endothelium-dependent coronary microvascular function and ultrastructure were examined after cardiopulmonary bypass, ischemic arrest, and reperfusion. During cardiopulmonary bypass, porcine hearts were arrested with either blood, albumin-crystalloid, or crystalloid cardioplegia for 1 hour, followed with reperfusion for 1 hour. Noninstrumented pigs were used as controls. Coronary microarterial vessels (90 to 190 microns in diameter) were studied in a pressurized, no-flow state with video microscopic imaging and electronic dimension analysis. Ischemic arrest with crystalloid cardioplegia markedly reduced endothelium-dependent relaxations to the adenine nucleotide adenosine diphosphate and the calcium ionophore A23187. Enhanced contractile responses were observed to the platelet-derived vasoactive substance serotonin and to the thromboxane A2 analogue U46619. Indomethacin corrected the enhanced contractile responses to serotonin, indicating the enhanced release of a constrictor prostanoid substance. Indomethacin had no effect on the impaired relaxations to adenosine diphosphate or A23187. Endothelium-dependent relaxations to adenosine diphosphate, serotonin, and A23187 were significantly preserved with either blood or albumin-crystalloid cardioplegia, whereas contractile responses to U46619 were normal. Endothelium-independent relaxation to nitroprusside was similar in all groups, indicating normal smooth muscle responsiveness. Electron microscopy revealed minimal alterations of vascular morphology of vessels in both crystalloid and blood cardioplegia groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasomotor Responses of Rat Coronary Arteries to Isoflurane and Halothane Depend on Preexposure Tone and Vessel Size

Background The authors previously reported that in rabbits, isoflurane exhibited a heterogeneous vasomotor effect, constricting small resistance coronary arteries and dilating larger conductance arteries. The novelty of isoflurane‐induced constriction of small coronary arteries raised the question of whether the finding depended on the unique experimental setup or species used. The purpose of this study was to address these questions. Therefore, a second species was studied, namely rats, as well as a second volatile anesthetic, halothane. In addition, the dependence of the vasomotor effect on the preexisting tone of the vessels was examined.

Epicardial and endocardial coronary microvascular responses: effects of ischemia-reperfusion.

Summary: To examine whether endocardial microvascular function is preferentially impaired by ischemia and reperfusion, we studied endothelium-dependent responses of epicardial and endocardial coronary microvessels (130–220 μm) from control pigs and from pigs subjected to 1-h regional myocardial ischemia (circumflex occlusion) followed by 1-h reperfusion (n = 8) in vitro using videomicroscopy. In control animals (n = 8), no significant transmural differences were apparent in microvascular responses to the endothelium-dependent agents bradykinin or the calcium ionophore A23187, to the endothelium-independent agent sodium nitroprusside (SNP), or to adenosine. Serotonin caused a slight but statistically insignificant greater relaxation of endocardial than of epicardial microvessels. After ischemia–reperfusion, relaxations to all endothelium-dependent agents (serotonin, bradykinin, A23187) and to adenosine were significantly reduced (p < 0.05 for all agents) as compared with the respective control responses. There were no significant differences between epicardial and endocardial responses in the ischemia-reperfusion group for any of the vasoactive agents. Endothelium-independent responses to SNP were not affected by ischemia–reperfusion, indicating no alteration in the ability of vascular smooth muscle to relax through guanylate cyclase-mediated mechanisms. Control epicardial microvascular responses were examined after endothelial denudation and after pretreatment with NG-monomethyl-l-arginine (l-NMMA), indomethacin, or glibenclamide. Control vessels denuded of endothelium demonstrated impaired responses to serotonin, bradykinin, A32187, and adenosine (p < 0.05 for all agents). Pretreatment of microvessels with l-NMMA reduced endothelium-dependent relaxations (p < 0.05), but did not alter responses to adenosine significantly. Indomethacin reduced relaxations to bradykinin, A23187, and adenosine (p < 0.05), and glibenclamide impaired adenosine responses (p < 0.05). Although the subendocardium is believed to be preferentially susceptible to ischemia, the microvascular dysfunction induced by ischemia–reperfusion is similar at epicardial and endocardial transmural levels. The diminished vasodilatory responses are probably related in large part to endothelial dysfunction with reduced production or release of nitric oxide (NO). Ischemia/reperfusion may also impair microvascular relaxation by altering production or release of prostaglandin substances from the endothelium or by damaging ATP-sensitive potassium channels on vascular smooth muscle.

Intrinsic Tone as Potential Vascular Reserve in Conductance and Resistance Vessels

BACKGROUNDnThe purpose of this study was to define the degree of intrinsic tone in conductance and resistance vessels, to define the calcium dependency of intrinsic tone in these vascular preparations, and to investigate the efficacy of vasodilatory agents on the level of intrinsic tone in these vascular preparations.nnnMETHODS AND RESULTSnAll vessels were deendothelialized. Isometric force was recorded from strips of ferret aorta, ferret pulmonary artery, and human coronary artery. Vessel diameter was recorded from the ferret epicardial coronary artery and from ferret coronary microvessel in a pressurized no-flow state. Intrinsic tone was defined as the active increase in force or decrease in diameter with warming from 6 degrees C to 37 degrees C. Changes in force or diameter with various pharmacological agents were expressed as a percentage of intrinsic tone. Our results indicate that intrinsic tone accounts for approximately 35% to 40% of total tone in all vascular preparations studied and is not dependent on extracellular calcium. Agents that increased cAMP levels (eg, forskolin, milrinone) and agents that decreased protein kinase C activity (eg, staurosporine) were partially effective in decreasing intrinsic tone. Nitroprusside, adenosine, hydralazine, and nifedipine had no significant effect.nnnCONCLUSIONSnOur results indicate that intrinsic tone represents a significant component of vascular tone that has not been previously recognized and remains largely unexploited by current pharmacological therapies.

Cocaine and the porcine coronary microcirculation: Effects of chronic cocaine exposure and hypercholesterolemia

OBJECTIVEnTo examine the acute effect of cocaine on the coronary microcirculation and whether chronic cocaine administration with or without a concomitant high-cholesterol diet affects beta-adrenoceptor and endothelial functions in the coronary microcirculation.nnnDESIGNnProspective experimental study.nnnSETTINGnLaboratory and animal research facility.nnnPARTICIPANTSnYorkshire pigs.nnnINTERVENTIONSnPigs were fed a high (2%)-cholesterol diet or a regular diet for 3 months. Animals in both groups received cocaine chronically (7 mg/kg/day, IM). Control animals were fed a regular diet.nnnMEASUREMENTS AND MAIN RESULTSnResponses of the porcine coronary arterioles (90 to 190 microns in diameter) were examined in vitro in a pressurized (40 mmHg) no-flow state using a video-imaging apparatus. Acute application of cocaine caused a significant contraction with a mean maximal diameter decrease of 14% +/- 5%, which was markedly reduced by muscarinic blockade but not significantly affected by alpha 1-adrenergic blockade. Lidocaine or procainamide had no vasoconstrictor effect. Chronic exposure of animals to cocaine diminished contractile responses to cocaine and reduced relaxation responses to the nonselective beta-adrenergic receptor agonist isoproterenol. Phenylephrine caused a minimal (< 4%) contraction of vessels in all groups. Chronic cocaine administration with concomitant high-cholesterol feeding attenuated endothelium-dependent relaxations to serotonin, whereas endothelium-dependent relaxations to bradykinin were unaffected. Endothelium-independent relaxations to sodium nitroprusside were similar in all groups.nnnCONCLUSIONSnThese results suggest that cocaine can exert a direct vasoconstrictor effect on the porcine coronary microcirculation via a muscarinic mechanism. Chronic exposure to cocaine significantly decreases beta-adrenoceptor-mediated relaxation and blunts endothelium-dependent relaxation to a small degree.

Isoflurane Attenuates cAMP-Mediated Vasodilation in Rat Microvessels

BACKGROUNDnEndothelium-dependent vasodilation mediated by cGMP is known to be attenuated by the inhalational anesthetic isoflurane. The present study examines the effect of isoflurane on beta-adrenergic and cAMP-mediated vasodilation.nnnMETHODS AND RESULTSnFifty-three subepicardial coronary arteries (diameter, 103 +/- 13 microns) from Wistar rats were studied in vitro in a pressurized (40 mm Hg), no-flow state with use of optical density video detection system. After preconstriction of vessels with the thromboxane A2 analogue U46619 10(-6) mol/L, concentration response curves to the nonselective beta-adrenergic agonist isoproterenol, the Gs protein activator sodium fluoride, the adenylate cyclase activator forskolin, the cAMP analogue 8-Br-cAMP, or the phosphodiesterase inhibitor RO20-1724 were obtained either in the presence of absence (control) of 2% isoflurane. Relaxations to all the agents tested were significantly reduced in the presence of isoflurane compared with controls.nnnCONCLUSIONSnIsoflurane attenuates cAMP-mediated vasodilation. The impairment appears to be distal to adenylate cyclase and is not due to enhancement of cAMP phosphodiesterase.

Pulmonary microvascular responses to protamine and histamine. Effects of cardiopulmonary bypass.

Total cardiopulmonary bypass with associated reduced pulmonary blood flow causes significant alterations of endothelium-dependent pulmonary microvascular responses after resumption of normal perfusion. To determine if this change in pulmonary vascular reactivity may influence the responses of pulmonary arterioles to protamine and histamine, we examined isolated pulmonary microvessels after cardiopulmonary bypass. Sheep were heparinized, cannulated, and placed on either total bypass without ventilation or partial bypass (70% of baseline pulmonary arterial flow) with continued ventilation. After 90 minutes, sheep were separated from cardiopulmonary bypass and the lungs were perfused normally for 60 minutes. Vessels from noninstrumented sheep were used as controls. Peripheral pulmonary arterioles (90 to 190 microns) were cannulated, pressurized (20 mm Hg) in a no-flow state, and examined with video microscopy. After precontraction of vessels with the thromboxane A2 analog U46619 by 18% to 25% of the baseline diameter, vasoactive agents were applied. Protamine sulfate, histamine, heparin, and the protamine-heparin complex caused significant dose-dependent relaxations of control pulmonary microvessels. These relaxation responses were substantially reduced or converted to contractile responses in endothelium-denuded vessels, which suggests that these relaxations are mediated through endothelium-dependent mechanisms. After partial bypass, responses to protamine and histamine were slightly reduced compared with the respective responses of control vessels, whereas the relaxation to protamine-heparin complex was not significantly altered. After total bypass, relaxation responses to protamine and protamine-heparin complex were markedly reduced, whereas histamine induced contraction of pulmonary microvessels. Endothelium-independent relaxation to sodium nitroprusside was not affected by partial cardiopulmonary bypass and was slightly reduced after total bypass. A reduced direct vascular relaxation response to protamine and increased contractile response to histamine (or other humoral substances released during the systemic administration of protamine sulfate) may contribute to the elevation of pulmonary vascular resistance during infusion of protamine after cardiopulmonary bypass.

Adenosine and AICA-riboside fail to enhance microvascular endothelial preservation

Crystalloid cardioplegia may cause coronary microvascular endothelial dysfunction during cardiopulmonary bypass. The perioperative administration of either adenosine or AICA-riboside (acadesine, 5-aminoimidazole-4-carboxamide-1-ribofuranoside) has been associated with improved myocardial functional preservation and improved coronary blood flow after ischemic arrest. To examine if this enhanced recovery of myocardial function and perfusion may be related to improved endothelial preservation, pigs were placed on cardiopulmonary bypass and the hearts were arrested with plain cold, hyperkalemic (K+ = 25 mmol/L) crystalloid cardioplegia, or cardioplegic solution containing either 0.1 mmol/L adenosine or 50 mumol/L AICA-riboside, which causes the release of endogenous adenosine. AICA-riboside (375 mg) also was infused over 30 minutes before cardioplegia in the later group. After 1 hour of ischemic cardioplegia, hearts were reperfused for 1 hour while the pigs were weaned from cardiopulmonary bypass. Coronary arterioles (90 to 190 microns in diameter) from both subepicardial and subendocardial regions of the left ventricle were studied in vitro in a pressurized, no-flow state with videomicroscopy. After contraction of vessels by 25% to 40% of the baseline diameter, drugs were applied extraluminally. Relaxation of control arterioles to serotonin was slightly greater in vessels from the subendocardial region compared with vessels from the subepicardial region, and subendocardial arterioles were more affected by cardioplegia than were subepicardial vessels. In contrast, relaxations of control microvessels to bradykinin and the calcium ionophore A23187 were similar in the two transmural myocardial regions. Responses to bradykinin and A23187 were significantly and similarly reduced after ischemic arrest with plain crystalloid cardioplegia.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary microvascular responses after exposure to iodinated contrast media.

Piana RN, Banitt PF, Nunez BN, Dai HB, Sellke FW. Coronary microvascular responses after exposure to iodinated contrast media. RATIONALE AND OBJECTIVES.Iodinated contrast media can cause a number of well-described acute hemodynamic and vascular effects including vascular spasm, hypotension, and arrhythmias. Coronary microvessels were studied in vitro after high-dose exposure to an ionic, high–osmolar contrast agent diatrizoate meglumine in vivo. The aim of this study was to examine the endothelium–dependent and endothelium-independent vasodilator responses of the microvessels after previous contrast media administration in a clinically relevant setting. METHODS.Left coronary angiography was performed on six pigs using a cumulative dose of 60 mL (5 mL/injection) of diatrizoate meglumine. After 1 hour of reperfusion, epicardial coronary microvessels were studied in vitro in a pressurized, no–flow state with video microscopy. The vasodilators bradykinin, calcium ionophore A23187, and sodium nitroprusside were sequentially applied extraluminally after preconstriction. Serotonin and the thromboxane A2 analog U46619 were studied without preconstriction. RESULTS.Microvessels exposed to diatrizoate meglumine had normal relaxation responses to the endothelium-dependent vasodilators bradykinin and calcium ionophore A23187 when compared to control vessels. The vasoconstrictor responses to U46619 and serotonin were not significantly altered compared to control vessels. Responses to the endothelium-independent vasodilator sodium nitroprusside were not reduced or were slightly enhanced after exposure to contrast media. CONCLUSION.Coronary resistance vessels responses to the endothelium–dependent vasodilators bradykinin and calcium ionophore A23187 are not diminished after previous exposure to diatrizoate meglumine. The vasoconstrictor responses to U46619 and serotonin were similarly unaffected by previous exposure to contrast media. This suggests that, when used in clinically relevant amounts, diatrizoate meglumine does not cause functional endothelium or vascular smooth muscle impairment.