The mechanisms of propofol-mediated hyperpolarization of in situ rat mesenteric vascular smooth muscle

Previously, we reported that propofol hyperpolarizes vascular smooth muscle (VSM) cells of small arteries and veins. The current study was designed to determine whether propofol-mediated hyperpolarization is the result of specific effects on potassium channels known to exist in VSM and on steps in the intracellular nitric oxide (NO), cyclic guanosine monophosphate (cGMP), and cyclic adenosine monophosphate (cAMP) second messenger pathways. VSM transmembrane potentials (E(m)) were measured in situ in sympathetically denervated, small mesenteric arteries and veins of Sprague-Dawley rats. Effects of propofol on VSM E(m) were determined before and during superfusion with specific inhibitors of VSM calcium-activated (K(Ca)), adenosine triphosphate-sensitive (K(ATP)), voltage-dependent (K(v)), and inward rectifying (K(IR)) potassium channels and with endogenous mediators of vasodilation. Propofol significantly hyperpolarized VSM in small mesenteric vessels. This hyperpolarization was abolished on inhibition of K(Ca) and K(ATP) channel activity and on inhibition of NO and cGMP (but not cAMP). Assuming a close inverse correlation between the magnitude of VSM E(m) and contractile force, these results suggest that propofol induces hyperpolarization and relaxation in denervated, small mesenteric vessels by activation of K(Ca) and K(ATP) channels. Such channel activation may be mediated by activation of NO and cGMP, but not cAMP, second messenger pathways. IMPLICATIONS: The results of this study indicate that propofol-mediated hyperpolarization in vascular smooth muscle can be attributed to the activation of calcium-activated, adenosine triphosphate-sensitive potassium channels, the nitric oxide, and cyclic guanosine monophosphate pathways.     

Pulmonary vascular changes induced by congenital obstruction of pulmonary venous return

BACKGROUND: Pulmonary venous obstruction (PVO) induces pulmonary arterial hypertension, as well as pulmonary venous hypertension, and jeopardizes the repair of cardiac lesions. METHODS: Four cases of congenital mitral stenosis and 4 cases of cor triatriatum (Lucas type A), ages ranging from 2 months to 16 years, were histologically examined on pulmonary vasculature. Histometrical analysis was performed on medial thickness and intimal changes of both pulmonary arteries and veins. For comparison, the examination of pulmonary vasculature in ventricular septal defect (VSD) cases was also performed. RESULTS: Medial thickening and intimal fibrosis, in both pulmonary arteries and veins with widespread lymphangiectasia, were characteristic vascular changes of PVO cases. Medial thickness of pulmonary arteries was correlated with preoperative pulmonary arterial pressure (PAP) (r = 0.77, p = 0.03 for systolic PAP), and greater than that of VSD cases. Medial thickness of pulmonary veins was also greater in PVO cases. Intimal fibrosis of pulmonary arteries and veins was seen extensively at the advanced ages, whereas no plexiform lesions or more advanced stages of pulmonary vascular disease were present. CONCLUSIONS: Congenital PVO induced progressive medial thickening and intimal fibrosis in pulmonary arteries and veins accompanied by lymphangiectasia. However, no plexiform lesions or more advanced stages of pulmonary vascular disease were present, which may explain the reversibility of pulmonary hypertension due to congenital PVO.     

Effects of isoflurane anesthesia on pulmonary vascular response to K+ ATP channel activation and circulatory hypotension in chronically instrumented dogs

BACKGROUND: The objective of this study was to evaluate the effects of isoflurane anesthesia on the pulmonary vascular responses to exogenous adenosine triphosphate-sensitive potassium (K+ ATP) channel activation and circulatory hypotension compared with responses measured in the conscious state. In addition, the extent to which K+ ATP channel inhibition modulates the pulmonary vascular response to circulatory hypotension in conscious and isoflurane-anesthetized dogs was assessed. METHODS: Fifteen conditioned, male mongrel dogs were fitted with instruments for long-term monitoring to measure the left pulmonary vascular pressure-flow relation. The dose-response relation to the K+ ATP channel agonist, lemakalim, and the pulmonary vascular response to circulatory hypotension were assessed in conscious and isoflurane-anesthetized (approximately 1.2 minimum alveolar concentration) dogs. The effect of the selective K+ ATP channel antagonist, glibenclamide, on the pulmonary vascular response to hypotension was also assessed in conscious and isoflurane-anesthetized dogs. RESULTS: Isoflurane had no effect on the baseline pulmonary circulation, but it attenuated (P<0.05) the pulmonary vasodilator response to lemakalim. Reducing the mean systemic arterial pressure to approximately 50 mm Hg resulted in pulmonary vasoconstriction (P<0.05) in the conscious state, and this response was attenuated (P<0.05) during isoflurane. Glibenclamide had no effect on the baseline pulmonary circulation, but it potentiated (P<0.05) the pulmonary vasoconstrictor response to hypotension in conscious and isoflurane-anesthetized dogs. CONCLUSIONS: These results indicate that K+ ATP-mediated pulmonary vasodilation and the pulmonary vasoconstrictor response to hypotension are attenuated during isoflurane anesthesia. Endogenous K+ ATP channel activation modulates the pulmonary vasoconstrictor response to hypotension in the conscious state, and this effect is preserved during isoflurane anesthesia.     

Cerebral blood flow and cerebral blood flow velocity during angiotensin-induced arterial hypertension in dogs

Pressure-passive perfusion beyond the upper limit of cerebral blood flow (CBF) autoregulation may be deleterious in patients with intracranial pathology. Therefore, monitoring of changes in CBF would be of clinical relevance in situations where clinical evaluation of adequate cerebral perfusion is impossible. Noninvasive monitoring of cerebral blood flow velocity using transcranial Doppler sonography (TCD) may reflect relative changes in CBF. This study correlates the effects of angiotensininduced arterial hypertension on CBF and cerebral blood flow velocity in dogs. Heart rate (HR) was recorded using standard ECG. Catheters were placed in both femoral arteries and veins for measurements of mean arterial blood pressure (MAP), blood sampling and drug administration. A left ventricular catheter was placed for injection of microspheres. Cerebral blood flow velocity was measured in the basilar artery through a cranial window using a pulsed 8 MHz transcranial Doppler ultrasound system. CBF was measured using colour-labelled microspheres. Intracranial pressure (ICP) was measured using an epidural probe. Arterial blood gases, arterial pH and body temperature were maintained constant over time. Two baseline measures of HR, MAP, CBF, cerebral blood flow velocity and ICP were made in all dogs (n = 10) using etomidate infusion (1.5 mg · kg^?1 · hr^?1) and 70% N₂O in O₂ as background anaesthesia. Following baseline measurements, a bolus of 1.25 mg angiotensin was injected iv and all variables were recorded five minutes after the injection. Mean arterial blood pressure was increased by 76%. Heart rate and ICP did not change. Changes in MAP were associated with increases in cortical CBF (78%), brainstem CBF (87%) and cerebellum CBF(64%). Systolic flow velocity increased by 27% and Vmean increased by 31% during hypertension (P < 0.05). Relative changes in CBF and blood flow velocity were correlated (CBF cortex — Vsyst: r = 0.94, CBF cortex — Vmean: r = 0.77; P < 0.001; CBF brainstem — Vsyst: r = 0.82, CBF brainstem — Vmean: r = 0.69; P < 0.05). Our results show that increases in arterial blood pressure beyond the upper limit of cerebral autoregulation increase CBF in dogs during etomidate and N₂O anaesthesia. The changes in CBF are correlated with increases in basilar artery blood flow velocity. These data suggest that TCD indicates the upper limit of the cerebral autoregulatory response during arterial hypertension. However, the amount of CBF change may be underestimated with the TCD technique.     

酚妥拉明对肝硬变门静脉高压症患者门静脉压力的影响

作者观察了１４例经病理确诊为坏死后肝硬变门静脉高压症患者及７例无肝脏疾病及肝脏转移的大肠癌患者周围静脉输入α肾上腺受体拮抗剂酚妥拉明前后肝静脉楔入压（ＷＨＶＰ）和门静脉压（ＰＶＰ）的变化情况。结果显示酚妥拉明能够有效地降低肝硬变门静脉高压症患者的ＷＨＶＰ和ＰＶＰ，（０．５６～０．６３ｋＰａ，０．４２～０．５０ｋＰａ，Ｐ＜０．０１），但同时对动脉舒张压和心率有一定影响（动脉舒张压下降０．９４～１．２７ｋＰａ，心率上升８．６７～１０．６７次／分），酚妥拉明对没有肝脏疾病和门静脉高压症的患者没有降低门静脉压力的作用。     

Comparison of hemodynamic changes induced by adenosine monophosphate and sodium nitroprusside alone and during dopamine infusion in the anesthetized dog

Adenosine receptor stimulation, such as by adenosine monophosphate (AMP), elicits systemic vasodilation that may be useful to control cardiac afterload during treatment of acute low-output cardiac failure. This study compared the hemodynamic effects of graded doses of sodium nitroprusside (SNP) with those of AMP when infused alone or in combination with the positive inotropic agent dopamine (DA) in anesthetized dogs. Both SNP (2-25 micrograms.kg-1.min-1) and AMP (200-2500 micrograms.kg-1.min-1) were effective vasodilators and reduced systemic vascular resistance and arterial pressure in a dose-dependent manner. Heart rate and cardiac index were increased by both agents. When compared at dosages that caused similar decreases in arterial pressure, cardiac index was increased more by AMP than by SNP. Also, AMP-induced vasodilation was associated with less tachyphylaxis. Sodium nitroprusside and AMP, at the dosages used, did not depress atrioventricular nodal conduction or antagonize DA-induced increases in renal blood flow. At equivalent decreases in mean arterial pressure, the increase from baseline in cardiac and stroke indices observed with AMP alone was further increased by the concomitant administration of DA. These results suggest that AMP and DA-AMP may offer significant advantages over SNP or DA-SNP in situations where elevation of cardiac output and reduction in afterload are required.     

A Comparison of the Hemodynamic Effects of Inotropic Agents

This experimental study was conducted to compare and contrast the cardiovascular effects of the drugs most commonly used to alleviate low-cardiac-output syndrome. Twenty-five adult mongrel dogs were infused with sodium pentobarbital (60 mg/min) until their cardiac output fell to 50 ± 5% of the average control values determined by thermodilution technique prior to pentobarbital infusion. The dogs were then divided into six groups, and one of the following agents or combinations of agents was administered to each group: isoproterenol, glucagon, dopamine, dobutamine, levarterenol and phentolamine, or levarterenol and nitroprusside.All drugs, except for glucagon and the combination of levarterenol and nitroprusside, produced an increase in cardiac output above the nonfailure baseline values. However, this increase was accompanied by an undesirable, pronounced tachycardia except when levarterenol was used simultaneously with phentolamine. Both dopamine and the combined infusion of levarterenol and phentolamine proved the most effective in restoring systemic arterial pressure to near baseline values, and both were able to increase renal blood flow above the failure baseline values. While renal blood flow remained elevated with all dosages of levarterenol and phentolamine, it tended to decrease with larger doses of dopamine.These experiments demonstrate that there are major advantages in the use of simultaneously infused levarterenol and phentolamine for control of low-cardiac-output syndrome: increased cardiac output without elevated peripheral vascular resistance, restoration of systemic arterial pressure and consequent improved coronary flow, absence of tachycardia, and augmented renal blood flow.     

Heterotopic auxiliary liver transplantation with portal flow. Gradual development of the collateral circulation

One of the causes of auxiliary liver transplantation failure is the inter-liver competition between the host liver and the graft for the hepatotrophic factors of the portal blood. We have developed an experimental model of heterotopic partial (30%) liver isotransplant using Wistar rats so as to study this competition. Splenoportography and dissection demonstrate the existence of collateral circulation. The collaterals at 90 days post-transplant (PT) consisted of veins from the portal vein to the host liver (PR), paraesophageal veins (PE) and splenorenal veins (SR). At 60 days P.T., PR and SR veins but not PE ones appeared, and at 30 days P.T., there were only PR veins. Graft atrophy at 90 days P.T. was associated with a severe degree of bile duct proliferation. The gradual development of portal hypertension causes porto-systemic collateral circulation and the graft loses the portal hepatotrophic factors. The late development of the portal hypertension and the biliary proliferation could be caused by the hepatic arterial ischemia in this experimental model. Thus, as has been described in the orthotopic liver transplantation, the heterotopic one might require a double vascularization, both portal and arterial.     

The Use of Levarterenol and Phentolamine in Patients with Low Cardiac Output Following Open-Heart Surgery

A study was made of the hemodynamic effects of levarterenol and phentolamine in patients in whom low cardiac output developed following open-heart operation. After the patients were weaned from cardiopulmonary bypass, the inotropic agents were infused into an external or internal jugular vein through an IVAC pump. Levarterenol was administered first until systolic arterial pressure rose 20 to 30% above the highest recorded preoperative pressure. After stabilization, phentolamine was administered, and infusion rates were adjusted so that arterial blood pressure was returned to levels measured before bypass.After infusion, all patients showed an increase in cardiac index, mean arterial pressure, mean stroke volume index, and left ventricular stroke work index. Mean pulmonary artery pressure, pulmonary vascular resistance, and left atrial pressure decreased in all patients.This study demonstrates that hemodynamic improvement occurs in humans in low cardiac output state with simultaneous infusion of levarterenol and phentolamine. We recommend these agents for use in patients with low output, unless they continue to receive propranolol during and after operation. Patients on a regimen of propranolol should not be given levarterenol and phentolamine.     

Influence of tumor size on anesthetic management for pheochromocytoma resection

The relationship between tumor size and the complexity of anesthetic management was studied using several values: plasma catecholamine concentrations, requirement of vasoactive agents, surgical time, blood loss, plasma glucose concentrations, and hemodynamic variables. Ten patients with clinical and laboratory diagnosis of pheochromocytoma were prospectively studied. Each anesthesia was maintained using inhalational anesthetic agents. Control of arterial blood pressure (ABP), heart rate (HR), and pulmonary artery blood pressure (PABP) was attempted with only titrating the inhalational anesthetics and adenosine triphosphate (ATP). If the titration of both the inhalational anesthetic and ATP failed to control ABP, HR, or PABP, then phentolamine, propranolol, trinitroglycerine, or norepinephrine was additionally used. Tumor weight was significantly correlated with amount of blood loss, surgical time, duration of ATP requirement, maximal dose of ATP infusion used, maximal plasma glucose concentration, and plasma total catecholamine concentration. However, the tumor weight was not correlated with hemodynamic variables. Patients who required propranolol generally had a significantly larger tumor than those who did not. In conclusion, surgical removal of large pheochromocytoma required more complicated anesthetic management than that of small pheochromocytoma.     

Alteration of blood flow distribution and vascular capacitance during induced hypotension in deafferented dogs

The effects of three hypotensive agents, sodium nitroprusside (SNP), nitroglycerin (NTG), and adenosine triphosphate (ATP), on blood flow distribution and vascular capacitance were examined in dogs anesthetized with sodium pentobarbital. To eliminate the modification by the baroreflex, carotid sinus was denervated and aortic and cardiopulmonary vagal fibers were sectioned. Total systemic circulation was divided into two parallel compartments, splanchnic (SP) and extra-splanchnic (ESP) vascular beds. Alteration of vascular capacitance was assessed by a change in systemic blood volume with constant cardiac output and constant venous pressure using a total heart-lung bypass. SNP- and ATP-induced hypotension caused blood flow redistribution from the SP to ESP beds, and this redistribution is greater (P less than 0.01) with ATP than that with SNP. In contrast, NTG-induced hypotension did not significantly cause redistribution. Systemic blood volume was increased during NTG- (10.4 +/- 2.2 ml/kg), and SNP-induced (4.8 +/- 1.1 ml/kg) hypotension. The increase by NTG was significantly greater (P less than 0.05) than that by SNP. In contrast, ATP-induced hypotension did not significantly change systemic blood volume. Since redistribution can result in a passive change in vascular capacitance, the differences in capacitance among SNP, NTG, and ATP can be explained in part by differences in redistribution of blood flow. Redistribution of blood flow from SP to ESP beds can increase venous return due to increasing the slope of the venous return curve. The results suggest that redistribution should be taken into consideration in evaluating the hemodynamic changes during induced hypotension.     

Responses of the skin microcirculation to acetylcholine in patients with essential hypertension and in normotensive patients with chronic renal failure

AIMS: To assess the endothelial function of the skin microcirculation in chronic renal failure (CRF) independent of hypertension, we investigated the changes of the cutaneous blood flow induced by iontophoretic delivery of acetylcholine (ACh) and of sodium nitroprusside (SNP) in CRF patients free from arterial hypertension and in patients with essential hypertension. METHODS: The study included 20 patients affected by CRF (mean creatinine clearance 12+/-2 ml/min) without arterial hypertension (mean blood pressure 96+/-1 mm Hg), 15 patients affected by essential hypertension (mean blood pressure 124 +/-1 mm Hg), and 20 normal controls. The changes of skin blood flow following iontophoretic delivery of ACh and of SNP were measured by laser Doppler flowmetry. RESULTS: Following maximal ACh or SNP delivery, the change of blood flow from the baseline was similar both in normals (683+/-92 vs. 684 +/- 87%) and in CRF patients (778+/-108 vs. 803+/-124%), whereas in the hypertensives the response to ACh was lower than to SNP (434+/-48 vs. 702 +/- 98%, p<0.01). Since the third ACh delivery dose, the skin blood flow increments were significantly lower in the hypertensive than in the CRF or in the normal control groups, whereas no difference was observed between uremics and controls. CONCLUSIONS: The endothelium-dependent hyperemia following ACh iontophoretic delivery is impaired in the skin microcirculation of essential hypertensive patients, but this is not the case in CRF patients with no history of arterial hypertension. This suggests that CRF per se, independent of arterial hypertension, is not associated with endothelial dysfunction of skin microcirculation.     

Halothane and Enflurane Attenuate Pulmonary Vasodilation Mediated by Adenosine Triphosphate-sensitive Potassium Channels Compared to the Conscious State

Background: Adenosine triphosphate (ATP)-sensitive potassium (K sup +ATP) channels play an important role in pulmonary vasoregulation. However, the effects of volatile anesthetics on K sup +ATP channel-mediated pulmonary vasoregulation have not been elucidated. The purpose of the present study was to investigate the effects of halothane and enflurane anesthesia on the pulmonary vasodilator response to the selective K sup +ATP channel agonist lemakalim (BRL38227) compared with that measured in the conscious state. The authors also investigated the extent to which endogenous neurohumoral vasoconstrictor mechanisms modulate the vasodilator response to K sup +ATP channel activation.

Method: Nineteen conditioned, male mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LPQ) relationship. LPQ plots were generated by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during gradual (approximately 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. After preconstriction with the thromboxane analog, U46619 (9,11-dideoxy-11alpha, 9alpha -epoxymethano-prostaglandin F2alpha), the pulmonary vascular dose-response relationship for the K sup +ATP agonist lemakalim was assessed in the conscious and halothane-anesthetized states and also in the conscious and enflurane-anesthetized states. This protocol was repeated in conscious and halothane-anesthetized dogs after combined neurohumoral block with antagonists of sympathetic alpha1 adrenoreceptors, arginine vasopressin V1 -receptors, and angiotensin II receptors. The effect of the K sup +ATP antagonist glybenclamide on the baseline LPQ relationship and on the lemakalim dose-response relationship also was assessed in conscious dogs.

Results: Compared with the conscious state, halothane, enflurane and glybenclamide had no net effect on the baseline LPQ relationship. In contrast, halothane and enflurane attenuated (P < 0.05) the pulmonary vasodilator response to lemakalim compared with the conscious state. Glybenclamide also caused a rightward shift (P < 0.05) in the lemakalim dose-response relationship. Combined neurohumoral block did not modulate the vasodilator response to lemakalim in the conscious state. The halothane-induced attenuation of the vasodilator response to lemakalim was apparent after combined neurohumoral block.     

前列腺素E1与硝普钠控制性降压对犬血流动力学影响的对比研究

对比研究了普鲁卡因复合麻醉下前列腺素Ｅ１（ＰＧＥ１）与硝普钠（ＳＮＰ）控制性降压时犬血流动力学变化。结果表明，ＳＮＰ降压组有显著的反射性心动过速和反跳性高血压，ＰＧＥ；降压组两者均无。ＰＧＥ１降压时心指数、肺动脉压等其它血流动力学参数亦比ＳＮＰ稳定，提示在保证心肌氧供求平衡及防止血管意外方面ＰＧＥ１降压优于ＳＮＰ。     

脱氢野百合碱诱导犬肺动脉高压模型的建立

目的用药物法建立犬肺动脉高压模型。方法野百合碱经脱氢处理成脱氢野百合碱 (dehydromonocrotaline,DMCT),经心导管注射入犬右心房,于注射药物后4周、8周测定肺动脉压力等血液动力学参数,并行肺组织病理检查,评估周围肺肌性动脉肌化情况、肌性肺动脉中膜肥厚程度。结果 DMCT(3 mg／kg)组8只犬存活2只,DMCT(2 mg／kg)组8只犬与对照组犬均存活。DMCT组4周后平均肺动脉压(mMPAP)(20．7±3．1)mm Hg(1 mm Hg=0．133 kPa),8周后mPAP(30．2±2．6)mm Hg,肺动脉收缩压(sPAP)和肺动脉楔压(PCWP)亦升高,与给药前相比,差异有统计学意义(P<0．01)。DMCT组8周后 mPAP、sPAP与PCWP亦明显高于溶剂对照组,差异有统计学意义,P<0．01。8周后DMCT组直径为15- 50μm的肺肌性动脉肌化数(54．3±6．6)％,直径为100-200μm的肺肌性动脉的中膜厚度百分比(27．3± 5．7)％,均高于溶剂对照组,差异有统计学意义(P<0．01),右心肥大指数增加(P<0．05)。光学显微镜下观察到DMCT组肺泡区肺肌性动脉中膜肥厚,新生内膜形成,管腔变小。结论 DMCT可成功诱导犬肺动脉高压模型,模拟人类终末期肺高压的病理特点。     

Continuous phentolamine perfusion in the treatment of severe arterial hypertension associated with neuroblastoma

Treatment of severe arterial hypertension associated with neuroblastoma is not well discussed in the literature. A six-month-old boy was referred for evaluation of an abdominal mass which proved to be neuroblastoma stage IV. Arterial hypertension of 26/16 kPa (190/110 mmHg) was also found. Because of the degree of malignancy and the risk of intra-tumoral haemorrhage, urgent management of the hypertension was required before proceeding to surgery. Phentolamine, a short-acting alpha-blocking agent, was administered as a continuous infusion of a 0.01 per cent solution, at a rate of 1 to 4 microgram X kg-1 X min-1 titrated according to the arterial blood pressure (BP), central venous pressure and urinary output. BP was rapidly controlled and the child went to surgery within 48 hours. The operation was uneventful but only 80 per cent of the tumour could be resected. Phentolamine was discontinued intraoperatively but was reinstituted postoperatively when hypertension recurred. With the return of normal intestinal function five days after surgery, phenoxybenzamine was begun p.o. and phentolamine was tapered over 24 hours and discontinued. A continuous infusion of phentolamine provided satisfactory control pre- and post-operatively with no significant hypotension. We consider this technique to be potentially very useful in the management of severe arterial hypertension associated with neuroblastoma, as it permits early surgical intervention under optimal conditions.     

Myocardial tissue oxygen during coronary artery constriction and hypotension in dogs

BACKGROUND: Sodium nitroprusside (SNP) may decrease myocardial tissue oxygenation in dogs with normal coronary arteries. We compared SNP- with desflurane-induced hypotension on myocardial tissue oxygen and pH in dogs with left anterior descending artery constriction. METHODS: Twenty-four dogs were anesthetized with 8% desflurane for baseline anesthesia. Catheters were inserted into the femoral artery and vein and the coronary sinus. A flow probe and flow restriction device was placed on the left anterior descending (LAD) artery. A probe that measured myocardial oxygen pressure was inserted into the middle myocardium in the LAD region. Baseline measures were made of LAD artery flow, arterial and coronary sinus blood gases, and myocardial tissue gases. A 30% decrease in blood pressure was induced with SNP with unrestricted LAD flow (n=6) or when LAD artery flow was restricted by 30% from baseline (n=6). In separate dogs, a 30% decrease in blood pressure was produced with 14 +/- 1% desflurane with unrestricted LAD flow (n=6) or with baseline LAD artery flow restricted by 30% (n=6). RESULTS: During SNP-induced hypotension with no LAD constriction, LAD artery flow and coronary sinus oxygen tension increased but myocardial tissue oxygen tension (PmO2) decreased by 40%. When baseline artery flow was decreased by 30% by LAD constriction, SNP-induced hypotension decreased tissue oxygen pressure by 80%, and ischemic acidosis was produced. During unrestricted LAD artery flow or with a 30% flow restriction, desflurane-induced hypotension produced no significant change from baseline myocardial tissue oxygen tension or pH. CONCLUSION: During coronary artery constriction, desflurane-induced hypotension maintained myocardial tissue oxygenation and pH better than did SNP-induced hypotension. The divergence between tissue and coronary sinus oxygen tension during SNP suggests that arteriovenous shunting may occur.     

Attenuation of arterial baroreceptor reflex response to acute hypovolemia during induced hypotension

Preservation of the arterial baroreflex response is important to restore cardiac output and blood pressure by reflex sympathetic nerve activation in the event of sudden hypotension caused by acute blood loss during surgery. However, the arterial baroreflex may be significantly attenuated by both anesthetics and hypotensive agents. In isoflurane-anesthetized dogs, the authors investigated the arterial baroreflex response 1) to bolus injections of sodium nitroprusside (SNP), prostaglandin E1 (PGE1) and trimethaphan (TM); and 2) to rapid blood loss (5 ml/kg) before and during induced hypotension with SNP, PGE1, and TM by measuring mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). Hypotension produced by both SNP and PGE1 was accompanied by an increase in RSNA and HR. The increase in RSNA and HR following the SNP bolus injection was significantly greater than that following injection of PGE1 (P less than 0.05). Trimethaphan was associated with a decrease in RSNA and HR. Rapid blood loss resulted in the same degree of MAP reduction (20 +/- 2 mmHg) before and during induced hypotension. Sensitivities of baroreflex, as evaluated by ratios of maximum changes in RSNA or HR to MAP (delta RSNA/delta MAP, delta HR/delta MAP), in response to rapid blood loss, were significantly suppressed during continuously induced hypotension, as compared with responses before induced hypotension. Despite the same degree of induced hypotension (70 +/- 5 mmHg of MAP), delta RSNA/delta MAP and delta HR/delta MAP in response to rapid blood loss were significantly greater with PGE1 than those with SNP (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular function during controlled hypotension induced by adenosine triphosphate or sodium nitroprusside in the anesthetized dog

The present study was undertaken to compare the hemodynamic effects of adenosine triphosphate (ATP) and sodium nitroprusside (NP) given in equieffective doses to induce hypotension during halothane anesthesia. Eight dogs, instrumented with pressure and ultrasonic dimension transducers for assessment of left ventricular (LV) performance, were given both NP and ATP. Regional blood flow was measured by radioactive microspheres. After 20 min of infusion, both drugs decreased systemic arterial pressure by 36% with minimal changes in cardiac index (CI), LV end-diastolic pressure, or heart rate. However, hypotension produced by ATP was associated with a greater CI (3.84 +/- 0.32 vs 2.97 +/- 0.35 L X min-1 X m-2) than was NP and also associated with a further decrease in systemic vascular resistance (14.4 +/- 1.4 vs 17.7 +/- 2.2 mm Hg X L-1 X min X m2). Left ventricular global function, measured by the slope of the linear regression line of the LV end-systolic pressure-diameter relation (Ees), did not change significantly after either drug. Blood flow to the coronary bed was significantly greater with ATP than with NP (231.6 +/- 30.6 vs 81.7 +/- 6.1 ml X min-1 X 100 g-1). Except for an increase in hepatic arterial blood flow with NP, neither ATP nor NP significantly altered blood flow to the brain, spinal cord, spleen, kidney, jejunum, muscle, and skin. Controlled hypotension by ATP was stable and rapidly reversible without rebound hypertension. The results of this study indicate that ATP is a rapidly acting, effective hypotensive agent that compares favorably with NP.     

Quantitative analysis of pulmonary vascular disease in total anomalous pulmonary venous connection in sixty infants.

A quantitative analysis of small pulmonary arteries, pulmonary veins, and lymphatic vessels was conducted in autopsy cases of total anomalous pulmonary venous connection. The materials were obtained from 60 cases of total anomalous pulmonary venous connection without asplenia or pulmonary stenosis, ages ranging from 2 days to 19 months at the time of death (mean age 2.2 months). Pulmonary arterial pressure had been measured in 32 of these patients before death. Twenty cases of ventricular septal defect with pulmonary hypertension and 15 normal individuals were used as the control group. The mean thickness of the media of small pulmonary arteries and veins was 12.7 and 7.6 microns, respectively, in the total anomalous pulmonary venous connection cases, both values being significantly larger than those for normal and ventricular septal defect cases. No changes in thickness with aging were found. Medial thickness in the arteries and veins was greater in the cases of pulmonary venous obstruction than in those without such obstruction. The medial thickness of small pulmonary arteries in total anomalous pulmonary venous connection cases correlated with increased pulmonary arterial pressure. When the patients with the same pulmonary arterial pressure levels were compared, the medial thickness was always greater in those who had total anomalous pulmonary venous connection than in those who had ventricular septal defect. The medial thickness of pulmonary veins was also highly correlated with increased pulmonary arterial pressure in total anomalous pulmonary venous connection. The severity of the intimal lesions was milder in those who had total anomalous pulmonary venous connection than in those who had ventricular septal defect, suggesting the protective role of the thickened pulmonary arterial media against development of intimal lesions. Intimal fibrous thickening of pulmonary veins was not seen in the cases of ventricular septal defect, but it was present in 45% of the total anomalous pulmonary venous connection cases. Lymphangiectasia was characteristically present in 62% of the total anomalous pulmonary venous connection cases. Interstitial emphysema was often a complication of lymphangiectasia, and it led to eight postoperative deaths.