Impact of cleft lip and/or palate in children on family quality of life before and after reconstructive surgery.

BACKGROUND: The aim of the study was to evaluate the impact of cleft lip/palate children together with consequent treatment on quality of family life using standardized questionnaire. Different to previous studies the evaluation of quality of family life by questionnaire was realized twice in the same group of families (before the reconstructive surgery and several months after palatoplasty). METHODS: The study was conducted in 40 families divided in two groups: 20 families with children with cleft lip (CL), 20 families with children with cleft lip and palate (CLP). The questionnaire of the Impact on Family Scale was used for evaluation of the influence of orofacial clefts on parent´s quality of life. Evaluations were made at the second month of child´s life and at one year of child´s life with reciprocally comparison. RESULTS: The higher impact of children with CLP on quality of family life was noted at 2 months and 1 year of child's age as compared to the impact of children with CL. The reduction of impact on quality of life after surgical correction was observed in families of children with CL at one year of child's age. This decrease of influence on family quality of life was due to significantly lower impact in strain and economic dimensions in families with CL children after operation. However, in the group of families with CLP children no significant changes in the impact on family quality of life were noted when compared to the values before and shortly after the reconstructive surgery. CONCLUSIONS: This study showed that orofacial clefts in children influence markedly the quality of their family life. The higher impact of children with CLP on quality of family life as compared to children with CL was noted and this impact in CLP group was not influenced shortly after reconstructive surgery. It is suggested that appropriate medical care in Cleft Centre with special psychological support may lead to improvement in quality of life for families with cleft lip and palate children (Tab. 2, Fig. 2, Ref. 14).

Mitochondrial ATP dependent potassium channels mediate non-ischemic preconditioning by tachycardia in dogs.

Brief episodes of tachycardia without myocardial ischemia prior to a coronary occlusion decrease myocardial infarct size in dogs. This non-ischemic preconditioning is mediated by adenosine. Because ischemic preconditioning is mediated through ATP dependent potassium channels, particularly the mitochondrial ones, we studied whether non-ischemic preconditioning is also mediated through these channels. In anesthetized dogs heart rate was kept constant at 120 cycles/min and aortic pressure changes were damped. Myocardial infarction was induced by occlusion of the anterior descending coronary artery for 60 min and reperfusion for 270 min. In a control group the infarct size (necrotic volume/risk region volume x 100) was 15.8+/-1.5%. Preconditioning with five periods of tachycardia, 5 min in duration each at 213 cycles/min with intervening periods of 5 min of basal heart rate at 120 cycles/min, reduced the infarct size by 45.6% (p < 0.05) with respect to the control group. This effect was completely reverted by the blockade of ATP dependent potassium channels with glibenclamide or 5 hydroxydecanoate (a specific blocker of mitochondrial ATP dependent potassium channels) prior to preconditioning. These effects were not due to differences in collateral flow, risk region size or hemodynamic variables between the groups. These results show that mitochondrial ATP dependent potassium channels mediate non-ischemic preconditioning by tachycardia in dogs.

Non-ischemic myocardial preconditioning.

The reduction of infarct size produced by brief ischemic episodes prior to a sustained occlusion of a coronary artery, called ischemic preconditioning, is a well known phenomenon that occurs in several species, but its mechanism is still under investigation. Recent reports support the idea that this protection can also be obtained by non-ischemic maneuvers like distention of the left ventricle and metabolic stimulation of myocardial cells. The features of non-ischemic preconditioning (temporal limitation, second window, tolerance development, remote preconditioning and efficiency of the protection), as opposed to those of ischemic preconditioning, are still to be determined. Neither is it known if non-ischemic preconditioning occurs in humans. From a physiological point of view the protective effect of an increase in metabolic rate of the heart means a constant feed-back mechanism in the myocardial cell that counteracts the presumptive damage consequent to the increase in metabolism. Therefore, in the presence of a sudden coronary occlusion the metabolic rate of the heart immediately before the occlusion would have a dual role of increasing the degree of ischemia and of protecting against it.

Tachycardia preconditions infarct size in dogs: role of adenosine and protein kinase C.

BACKGROUND: Myocardial ischemic preconditioning is a well-known phenomenon, however there is scant information in regard to nonischemic preconditioning. METHODS AND RESULTS: We studied in anesthetized dogs the preconditioning effect of tachycardia and the mediation of adenosine and protein kinase C in this process. In a control group the anterior descending coronary artery was occluded for 60 minutes and reperfused for 270 minutes. Heart rate was kept constant at 120 +/- 5 cycles/min and aortic pressure changes were damped. The infarct size (necrotic volume/risk region volume x 100) was 15.8 +/- 1.5%. In another group of dogs a similar protocol was followed, but five periods of tachycardia (213 +/- 12 cycles/min), 5 minutes in duration each, with 5 minutes of intervening periods at control heart rate, were induced previous to the coronary occlusion. The infarct size was reduced by 46% (P<.001) with respect to the nonpreconditioned group. This effect was not due to changes in collateral flow nor risk region size. During tachycardia, myocardial interstitial adenosine increased about twofold (P<.05); no metabolic, hemodynamic, or ECG evidences of ischemia were observed and the transmural vasodilatory reserve was preserved. The blockade of adenosine receptors with 8 phenyltheophylline, before or after the preconditioning tachycardia, reverted its protecting effect but it did not modify infarct size in nonpreconditioned dogs. No changes in cytosolic or particulate protein kinase C activity or translocation of alpha-, beta-, epsilon-, and zeta- protein kinase C isozyme by effect of tachycardia or ischemia were observed between preconditioned and nonpreconditioned dogs. CONCLUSIONS: Tachycardia, in the absence of ischemia, mimics the preconditioning effect of ischemia in the dog. This effect is mediated by adenosine but not by changes in protein kinase C activity or its translocation.

Effect of transthoracic electric current on the coronary circulation of the dog.

OBJECTIVE: In vitro experiments have shown that an electric field changes coronary vascular resistance (CVR) tone and damages the vascular endothelium. The effect of transthoracic electric current in dogs on the vasodilatory responses mediated through the endothelium and reactive hyperemia were studied. The manner of delivery of the electric current was similar to that used clinically during cardiac resuscitation. DESIGN: Eight mongrel dogs of either sex weighing between 15 and 22 kg were anesthetized with sodium pentobarbital. The lungs were mechanically ventilated and the thorax was opened. Circumflex coronary flow was measured with an electromagnetic flowmeter. Mean aortic pressure and the heart rate were kept constant and left ventricular systolic and diastolic pressures did not change during the procedures. The changes in CVR produced by different intracoronary doses of acetylcholine and reactive hyperemia to 10 and 30 s of circumflex coronary occlusion were measured before and after the transthoracic delivery of five synchronized electric shocks, 300 J each 1 min apart. MAIN RESULTS: CVR decreased by 32.8 +/- 2.1% (P < 0.01) from the effects of the electric shocks in spite of no changes in heart rate, ventricular systolic and diastolic pressures nor left ventricular oxygen consumption. After the delivery of the electric shocks, the vasodilatory response to acetylcholine decreased by a mean value of 35.9 +/- 2.6% for the different doses (P < 0.001) and reactive hyperemia decreased by 42.5 +/- 5.5% (P < 0.001) and by 31.5 +/- 9.6% (P < 0.02) for the 10 and 30 s occlusion duration, respectively. The intracoronary infusion of sodium nitroprusside decreased the coronary vascular resistance to a minimal value lower than that obtained by the maximal dose of acetylcholine but similar to before and after the passage of the electrical current revealing the preservation of the coronary vasodilatory reserve after the electrical shocks. CONCLUSIONS: These results show that transthoracic electrical shocks as used clinically induce coronary vasodilation but simultaneously produce endothelial dysfunction.

Relative participation of adenosine and endothelium derived mediators in coronary reactive hyperemia in the dog.

The metabolites that mediate coronary reactive hyperemia have not been definitely identified. Although adenosine and endothelium derived substances seem to be involved, their relative contributions have not been defined yet. In the canine coronary circulation, we studied the relative participation of adenosine, nitric oxide and prostacyclin in reactive hyperemia, by measuring the changes produced by interfering with the synthesis or action of these metabolites. The dose-response curve for flow changes vs intracoronary administration of adenosine was displaced to the right after the inhibition of nitric oxide synthesis with N-omega-nitro-L-arginine, revealing that nitric oxide release partly mediates the vasodilator action of adenosine. The inhibition of PGI-2 synthesis with indomethacin did not modify reactive hyperemia. Interference with adenosine action, by administration of adenosine deaminase plus theophylline, decreased reactive hyperemia by 31.0 +/- 4.0% (p < 0.001). Inhibition of nitric oxide synthesis decreased reactive hyperemia by a larger (p < 0.005) magnitude, 41.0 +/- 3.9% (p < 0.001), revealing the existence of other stimuli for nitric oxide release in reactive hyperemia besides adenosine. Simultaneous inhibition of nitric oxide and PGI-2 syntheses and of adenosine action reduced reactive hyperemia, but the effect was not additive, reaching 49.5 +/- 4.5% of control. Since nitric oxide and adenosine are the most important mediators in reactive hyperemia so far described, our results suggest that other metabolites, acting directly or through mediators other than adenosine or nitric oxide, are responsible for about 50% of coronary reactive hyperemia.

Relative participation of adenosine and endothelium derived mediators in coronary reactive hyperemia in the dog

The metabolites that mediate coronary reactive hyperemia have not been definitely identified. Although adenosine and endothelium derived substances seem to be involved, their relative contributions have not been defined yet. In the canine coronary circulation, we studied the relative participation of adenosine, nitric oxide and prostacyclin in reactive hyperemia, by measuring the changes produced by interfering with the synthesis or action of these metabolites. The dose-response curve for flow changes vs intracoronary administration of adenosine was displaced to the right after the inhibition of nitric oxide synthesis with N-omega-nitro-L-arginine, revealing that nitric oxide release partly mediates the vasodilator action of adenosine. The inhibition of PGI-2 synthesis with indomethacin did not modify reactive hyperemia. Interference with adenosine action, by administration of adenosine deaminase plus theophylline, decreased reactive hyperemia by 31.0 +/- 4.0 percent (p < 0.001). Inhibition of nitric oxide synthesis decreased reactive hyperemia by a larger (p < 0.005) magnitude, 41.0 +/- 3.9 percent (p < 0.001), revealing the existence of other stimuli for nitric oxide release in reactive hyperemia besides adenosine. Simultaneous inhibition of nitric oxide and PGI-2 syntheses and of adenosine action reduced reactive hyperemia, but the effect was not additive, reaching 49.5 +/- 4.5 percent of control. Since nitric oxide and adenosine are the most important mediators in reactive hyperemia so far described, our results suggest that other metabolites, acting directly or through mediators other than adenosine or nitric oxide, are responsible for about 50 percent of coronary reactive hyperemia

Endothelium-derived relaxing factor participates in the transmural distribution of coronary bloodflow.

OBJECTIVE: To study the role of endothelium-derived relaxing factor (EDRF)--which participates in the regulation of coronary vascular tone, but has an unknown role in the transmural distribution of coronary flow--in transmural coronary flow distribution during steady basal flow and during reactive hyperemia in the left ventricular wall of the dog. DESIGN: Sixteen mongrel dogs of either sex weighing between 14 and 24 kg were anesthetized with sodium pentobarbital. The lungs were mechanically ventilated and the thoraces were opened. Circumflex coronary flow was measured with an electromagnetic flowmeter, and its transmural distribution across four layers of the left ventricular wall was measured with radioactive microspheres. Measurements were done during steady basal flow and during peak reactive hyperemia before and after the inhibition of the EDRF synthesis with N-omega-nitro-L-arginine (NNLA). Mean aortic and systolic left ventricular pressures and heart rate were kept constant, and left ventricular end-diastolic pressure increased by only 3.3 mmHg during reactive hyperemia. MAIN RESULTS: NNLA produced a mean decrease of steady basal flow of 22.3 +/- 0.9% (P < 0.01). Flow decreased in all layers of the wall; the decrease, however, was proportionally less in the subendocardium (P < 0.05). During reactive hyperemia (before NNLA), flow was redistributed to the subendocardium (compared with steady basal flow). Administration of NNLA reduced the magnitude of peak reactive flow to all layers in the wall, showing a relative enhancement of flow in the subendocardium. CONCLUSIONS: These results suggest that the EDRF participates in the regulation of coronary bloodflow and its distribution across the left ventricular wall.

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-omega-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.

[Endothelium and coronary circulation]. / El endotelio y la circulacion coronaria.

In the last few years, so many different substances produced by the endothelium have been discovered that this structure is considered today a paracrine organ. Among these substances, there are at least three with marked vascular effects: prostacyclin (PGI-2) and the endothelium-derived relaxing factor (EDRF) are vasodilators, platelet stabilizers and anti-atherogenic. On the other hand, endothelin-1 (ET-1) is a potent vasoconstrictor and probably pro-atherogenic. There are many agents that stimulate the liberation of these substances by the endothelium and most of them stimulate simultaneously the production of the three substances. Even though it is not possible yet to define the exact participation of the endothelium in the normal regulation of coronary blood flow it is highly probably that a disfunction of this structure secondary to hypercholesterolemia, hypertension, atheromatosis, diabetes and smoking may decrease the coronary reserve, induce coronary spasm and facilitates the development of atheroma.

Effect of endothelin on total and regional coronary resistance 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.

Effect of left intraventricular pressure on magnitude of vascular waterfall in the epicardial coronary veins.

STUDY OBJECTIVE: The aim was to test the hypothesis of a vascular waterfall in the epicardial veins due to compression by the left ventricular (LV) pressure. If this were so, the epicardial venous pressure should be a direct function of the LV pressure. DESIGN: Canine arrested hearts were used, without autoregulation and perfused with the Langendorff technique. Coronary flow and outflow pressure were measured in the great cardiac vein, which was the only outflow of the system. The pressure in an epicardial vein was also measured. The measurements were done with LV pressures varying from zero to 40 mm Hg. The outflow pressure was progressively increased until a steady decrease in flow occurred. This pressure was considered the critical outflow pressure. EXPERIMENTAL MATERIAL: 19 mongrel dogs, 18-25 kg, were used. The animals were anaesthetised and the hearts perfused in the Langendorff manner with homologous blood. MEASUREMENTS AND MAIN RESULTS: The epicardial venous pressure before outflow pressure was increased was higher than LV pressure (even at zero LV pressure), and increased linearly with the increase in LV pressure (epicardial venous pressure = 0.74 LV pressure +6.18; r = 0.93). The increase in outflow pressure did not modify flow until it reached a value (critical outflow pressure) similar to epicardial venous pressure. Critical outflow pressure was linearly related to LV pressure (critical outflow pressure = 0.65 LV pressure +5.13, r = 0.87). CONCLUSIONS: The results support the hypothesis of a waterfall circulation in the epicardial veins during diastole, the magnitude of which is a function of the LV pressure.

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

The vasoactive effect of neuropeptide Y (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-1.100 g-1 without changes in myocardial oxygen consumption. The potency of NPY as a coronary vasoconstrictor was about 250 times that of noradrenaline. Pretreating the coronary 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 microM 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.

Effects of alpha-1 adrenergic blockade on regional flow in the ischemic heart.

Although ischemia induces strong coronary vasodilation, some vasoconstrictive tone persists in the ischemic myocardium. To assess whether this tone is mediated through alpha adrenergic receptors, coronary blood flow was measured with radioactive microspheres in the normal and in the ischemic left ventricular wall of the dog before and during alpha blockade with Trimazosin. Ischemia was accomplished by decreasing the coronary perfusion pressure to 22 +/- 1.4 mmHg. Heart rate and aortic pressure were kept constant in each experiment. Trimazosin significantly increased flow in the normal left ventricular wall, but to a greater extent in the subepicardium than in the subendocardium with a decrease of the inner/outer flow ratio from 1.38 +/- 0.12 to 1.20 +/- 0.11 (p less than 0.05). In the ischemic region, Trimazosin did not change total transmural flow, but flow decreased in the subendocardium and increased in the subepicardium with a decrease in the inner/outer flow ratio from 0.63 +/- 0.09 to 0.38 +/- 0.06 (p less than 0.01). These results show that a vasoconstrictive tone mediated through alpha-1 adrenergic receptors persists in the ischemic myocardium, the blockade of which is detrimental for the subendocardium.

Effects of alpha-1 adrenergic blockade on regional flow in the ischemic heart.

Although ischemia induces strong coronary vasodilation, some vasoconstrictive tone persists in the ischemic myocardium. To assess whether this tone is mediated through alpha adrenergic receptors, coronary blood flow was measured with radioactive microspheres in the normal and in the ischemic left ventricular wall of the dog before and during alpha blockade with Trimazosin. Ischemia was accomplished by decreasing the coronary perfusion pressure to 22 +/- 1.4 mmHg. Heart rate and aortic pressure were kept constant in each experiment. Trimazosin significantly increased flow in the normal left ventricular wall, but to a greater extent in the subepicardium than in the subendocardium with a decrease of the inner/outer flow ratio from 1.38 +/- 0.12 to 1.20 +/- 0.11 (p less than 0.05). In the ischemic region, Trimazosin did not change total transmural flow, but flow decreased in the subendocardium and increased in the subepicardium with a decrease in the inner/outer flow ratio from 0.63 +/- 0.09 to 0.38 +/- 0.06 (p less than 0.01). These results show that a vasoconstrictive tone mediated through alpha-1 adrenergic receptors persists in the ischemic myocardium, the blockade of which is detrimental for the subendocardium.

Changes in total and transmural coronary blood flow induced by ethanol.

We studied the effects of ethanol on total coronary resistance and on the resistance across the left ventricular wall in the isolated empty beating heart of the dog. The coronaries were perfused with homologous fresh blood, thermoregulated at 37 degrees C and equilibrated with a gas mixture of O2 (95%) and CO2 (5%). Coronary flow distribution was measured with radioactive microspheres. In 22 experiments in which coronary flow was kept constant, ethanol (calculated concentration in the perfusing blood, 2.9 +/- 0.2 g . litre-1) produced a significant decrease in perfusion pressure (from 14.2 +/- 0.5 to 11.9 +/- 0.5 kPa, P less than 0.005). This decrease in perfusion pressure was not caused by metabolic autoregulation since ethanol produced a decrease in the oxygen consumption of the heart (2.19 +/- 0.43 to 1.62 +/- 0.31 cm3 . min-1 . 100 g-1, P less than 0.05). It was not caused, either, by a decrease in extravascular compression since ethanol did not produce any further decrease in perfusion pressure after maximal dilatation of the coronaries with dipyridamole. In experiments performed either at constant coronary flow or at constant perfusion pressure, flow across the left ventricular wall was redistributed towards the subendocardium during the vasodilatory effect of ethanol. Since in our experimental conditions, changes in the neurohumoral, metabolic and cardiac mechanical factors that influence coronary flow were discarded, this study demonstrates a direct vasodilatory effect of ethanol on the coronary vessels with a redistribution of flow towards the subendocardium.

Effects of alpha-adrenergic receptor blockade on coronary circulation in conscious dogs.

The effects of three alpha-adrenergic-receptor blocking agents (phentolamine, prazosin, and trimazosin) were compared on the coronary circulation and left ventricular (LV) function in chronically instrumented conscious dogs. The three alpha-adrenergic-receptor blocking agents were administered in equidepressor doses (mean arterial pressure fell by approximately 20%) and in the presence of beta-adrenergic-receptor blockade and constant heart rate. LV systolic pressure, LV end-diastolic pressure, and LV end-diastolic diameter also fell similarly with the three drugs. Phentolamine decreased the time rate of change of LV pressure (LV dP/dt) by 21 +/- 3%, whereas trimazosin and prazosin decreased LV dP/dt only by 14 +/- 2 and 11 +/- 2%, respectively. LV velocity was not changed with trimazosin and prazosin but decreased with phentolamine by 12 +/- 4%. The three drugs exerted differential effects on the coronary circulation. Only trimazosin increased coronary blood flow (18 +/- 5%). Trimazosin decreased late diastolic coronary resistance (LDCR) by 35 +/- 2%, which was significantly more than reductions in LDCR induced by prazosin (22 +/- 2%) and by phentolamine (11 +/- 3%). A test dose of phenylephrine (5.0 micrograms/kg) increased mean arterial pressure by 53 +/- 3.5 mmHg. After trimazosin, prazosin, and phentolamine, the same dose of phenylephrine increased mean arterial pressure by 24 +/- 2.1, 14 +/- 1.6, and 1.9 +/- 0.6 mmHg, respectively. The response after phentolamine was significantly less than with trimazosin (P less than 0.01) and prazosin (P less than 0.02). Thus the capacity of these three alpha-adrenergic-receptor blocking drugs to dilate coronary vessels is inversely proportional to their capability to block exogenous alpha-adrenergic-receptor agonists.

Regulation of large coronary arteries by beta-adrenergic mechanisms in the conscious dog.

We examined, in conscious dogs, the effects of beta-adrenergic stimulation on measurements of left circumflex coronary arterial diameter and blood flow and on calculations of late diastolic coronary resistance (LDCR) and left circumflex coronary internal cross-sectional area (CSA). Isoproterenol (0.1 microgram/kg) initially decreased mean arterial pressure by 25 +/- 2% (mean +/- SEM), and LDCR by 62 +/- 4%, and increased heart rate by 82 +/- 10%, left ventricular (LV) dP/dt by 79 +/- 12%, and mean coronary blood flow by 85 +/- 5%, while CSA rose slightly. The peak effects on CSA (24 +/- 2%) occurred later, along with decreases in mean arterial pressure (7.4 +/- 1.0%) and LDCR (25 +/-5.3%) and increases in coronary blood flow (14 +/- 2%), LV dP/dt (12 +/- 3%), and heart rate (24 +/- 4%). Pirbuterol (1.0 microgram/kg) induced changes that were qualitatively similar to those induced by isoproterenol. Prenalterol (20 micrograms/kg), a cardioselective beta 1-adrenergic receptor agonist, did not affect mean arterial pressure, but increased heart rate by 40 +/- 5%, LV dP/dt by 72 +/- 10%, mean coronary blood flow by 34 +/- 11%, and CSA by 26 +/- 3%, and decreased LDCR by 29 +/- 5+. Isoproterenol and pirbuterol, but not prenalterol, increased coronary sinus O2 content and decreased A-VO2 difference. After beta 1-adrenergic receptor blockade with atenolol (1 mg/kg), prenalterol no longer induced significant effects, whereas isoproterenol and pirbuterol decreased mean arterial pressure similarly to what was observed prior to blockade, but did not increase LV dP/dt, and induced attenuated increases in mean coronary blood flow, CSA, and decreases in LDCR. Thus, in the intact, conscious animal, large coronary arteries are regulated by beta-adrenergic mechanisms. Surprisingly, a major fraction of large coronary arterial dilation appeared to be either directly or indirectly due to beta 1-adrenergic receptor mechanisms, although beta 2-adrenergic effects were also significant.

Effects of prazosin on coronary and left ventricular dynamics in conscious dogs.

The left ventricular (LV) and coronary vascular effects of prazosin, a drug that reduces peripheral vascular resistance by blocking postsynaptic alpha receptors, were examined in conscious dogs. Prazosin, 0.07 mg/kg/min i.v. for 7 minutes, induced sustained hypotensive effects for more than 12 hours. The peak effects occurred 30-45 minutes after administration. Prazosin increased heart rate by 28 +/- 9%, did not change mean coronary blood flow significantly, decreased mean arterial pressure by 15 +/- 4%, LV end-diastolic diameter by 10 +/- 2%, LV end-systolic diameter by 8 +/- 2%, late diastolic coronary resistance by 22 +/- 7%, and LV dP/dt by 9 +/- 4%. These effects of prazosin were not altered substantially by maintaining heart rate constant with electrical pacing or by pretreatment with beta-adrenergic blockade. However, after chronic reserpine treatment, prazosin did not reduce either mean arterial pressure or late diastolic coronary resistance. The alpha-blocking properties of the drug were established when prazosin attenuated pressure responses to phenylephrine, norepinephrine and bilateral carotid occlusion. Thus, in conscious dogs with heart rate constant, prazosin, by blocking alpha-adrenergic receptors, induces prolonged coronary vasodilation associated with reductions in the major determinants of myocardial oxygen consumption, e.g., arterial and LV pressures, LV end-diastolic diameter and LV dP/dt. However, the coronary vasodilation was not intense enough to increase coronary blood flow above control levels.