The pulmonary hemodynamic changes under experimental myocardial ischemia in rabbits following beta-adrenoreceptors blockade

In acute experiments in anesthetized rabbits, changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied as well as in control animals and after the blockade of beta-adrenoreceptors. The myocardial ischemia decreased the left ventricular myocardial contractility, cardiac output and arterial pressure, decreased the pulmonary artery pressure and flow. Following myocardial ischemia, the pulmonary artery pressure decreased less than pulmonary artery blood flow as the result of elevating of the left atrial pressure, meanwhile pulmonary vascular resistance was not changed. Following myocardial ischemia in animals after the blockade of the beta-adrenoreceptors, the pulmonary flow decreased the same as in control animals. However, the pulmonary artery pressure was decreased twofold more significantly than in control animals, and its diminishing was in the same degree as the pulmonary artery flow. Following myocardial ischemia after the blockade of the beta-adrenoreceptors, the pulmonary vascular resistance decreased whereas the left atrial pressure did not change significantly because the myocardial contractility decreased less than in control animals.     

The pulmonary hemodynamics changes under experimental myocardial ischemia in rabbits following increased arterial pressure

In acute experiments in anesthetized rabbits, changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied in control animals and after the infusion of adrenaline and phenylephrine. The pulmonary artery pressure was increased following infusion of these drugs; however, it decreased to normal level in the condition of myocardial ischemia. Meanwhile the pulmonary vascular resistance was elevated to the same level in both cases. Following adrenaline infusion, the pulmonary artery blood flow and venous return increased and, in the condition of myocardial ischemia, they decreased to normal level, but the left atrial pressure was decreased. Following phenylephrine infusion, the pulmonary artery blood flow and venous return did not change and, in the condition of myocardial ischemia, these parameters decreased lower than normal level but the left atrial pressure was elevated. Thus we concluded that equal values of the pulmonary artery pressure in both cases were caused by changes of different character in the left atrial pressure. The differences of the changes character and values of the pulmonary artery flow under experimental myocardial ischemia following the infusion of adrenaline and phenylephrine were caused by different shifts of the venous return.     

Relations between changes of the pulmonary and systemic hemodynamics following neurogenic stimuli

The character and values of changes of the pulmonary and systemic hemodynamics following neurogenic stimuli application on the cardiovascular system were studied in acute experiments on the anesthetized cats. Vagus nerve stimulation reduced the heart rate and decreased myocardial contractility in result, right and left atrial pressure increased, whereas pulmonary pressure and flow, venous return, cardiac output and venous return decreased. Pulmonary pressure reached maximal level and returned to the initial value earlier than the pulmonary flow. On the contrary, pulmonary pressure, following neurogenic pressor stimuli, reached maximal level and returned to the initial value later than the pulmonary flow; the sign of the changes of the pulmonary pressure could be positive or negative, whereas pulmonary flow were always increased. The venous return did not change, and for this reason it could not cause the increasing of pulmonary flow which was elevated following increasing of the heart rate and myocardial contractility. The shifts of the pulmonary pressure were correlated with the pulmonary resistance those, which were increased after the stellate ganglion stimulation and decreased following carotid reflex; they did not change in case of sciatic nerve stimulation. The shifts of the pulmonary pressure did not depended on the decreased right and left atrial pressures. When the pulmonary flow was always increased, the cardiac output following electrical stimulation of the stellate ganglion and sciatic nerve was elevated, and it was decreased following carotid reflex, i. e. linear correlation between these parameters were not found. Pulmonary and systemic arterial pressure changes were more obvious in case of direct neurogenic stimuli application comparing with reflectory ones; in both cases, the positive chrono- and inotropic cardiac effects were similar.     

Specificity of autonomic influences on cardiac responses during myocardial ischemia.

A possible role of the autonomic nervous system in the left ventricular response to acute regional myocardial ischemia was sought in conscious dogs instrumented for measurement of left ventricular pressure, internal diameter, and aortic flow. Ischemia produced by occluding the left circumflex coronary artery caused tachycardia and reduced contractility. Changes during control occlusions were compared with those during occlusion.s after beta-adrenergic blockade, parasympathetic blockade, and combined sympathetic and parasymphatetic blockade. Beta-blockade did reduce the tachycardia and slightly reduced left ventricular diameter changes in response to coronary occlusion. Results obtained in animals following surgical cardiac sympathectomy indicated reduced tachycardia and no effects on other parameters. The principal effect of parasympathetic blockade was to augment the increase in end diastolic diameter during occlusion Right atrial pacing indicated this change was due to higher initial heart rates. Combined parasympathetic and sympathetic blockade did not alter inotropic responses to coronary occlusion. Results indicated that inotropic support due to changes in activity in autonomic nerves is not increased during acute occlusion of the left circumflex coronary artery.     

Acidaemia reduces cardiac output and left ventricular contractility in conscious lambs

We studied the effects of HCI-induced metabolic acidaemia on cardiac output, contractile function, myocardial blood flow, and myocardial oxygen consumption in nine unanaesthetized newborn lambs. Through a left thoracotomy, catheters were placed in the aorta, left atrium and coronary sinus. A pressure transducer was placed in the left ventricle. Three to four days after surgery, we measured cardiac output, dP/dt, left ventricular end diastolic and aortic mean blood pressures, heart rate, aortic and coronary sinus blood oxygen contents, and left ventricular myocardial blood flow during a control period, during metabolic acidaemia, and after the aortic pH was restored to normal. We calculated systemic vascular resistance, myocardial oxygen consumption and left ventricular work. Acidaemia was associated with reduction in cardiac output, maximal dP/dt, and aortic mean blood pressure. Left ventricular end diastolic pressure and systemic vascular resistance increased, and heart rate did not change significantly. The reduction in myocardial blood flow and oxygen consumption was accompanied by fall in cardiac work. Cardiac output returned to control levels after the pH had been normalized but maximal dP/dt was incompletely restored. Myocardial blood flow and oxygen consumption increased beyond control levels. This study demonstrates that HCI-induced metabolic acidaemia in conscious newborn lambs is associated with a reduction in cardiac output which could have been mediated by the reduction in contractile function and/or the increase in systemic vascular resistance. The decreases in myocardial blood flow and oxygen consumption appear to reflect diminished cardiac work. The restoration of a normal cardiac output after normalization of the pH appears to have resulted from the increases in heart rate and left ventricular filling pressures in conjunction with an incomplete restoration of contractile function.     

Proteasome inhibition 1 h following ischemia protects GRK2 and prevents malignant ventricular tachyarrhythmias and SCD in a model of myocardial infarction

Arrhythmia-prone epicardial border zone (EBZ) tissues demonstrate decreased G protein-coupled receptor kinase-2 (GRK2) activity and increased sensitivity to isoproterenol 6-24 h after coronary artery ligation in the dog. We previously demonstrated that the ischemia-mediated decrease in GRK2 in cardiac ischemic tissue was largely blocked by proteasome blockade initiated 1 h before the onset of ischemia, and this was associated with significant cardioprotection against malignant ventricular tachyarrhythmias. For application to clinical circumstances, it is desirable to determine whether a clinical window exists following the onset of ischemia for such a protective effect. The treatment of six dogs with the selective proteasome inhibitor bortezomib 1 h after the surgical induction of left coronary artery ischemia provided 80% (EBZ) and 42% (infarct) protection (by immunoblot) against the loss of GRK2 at 24 h. There was no significant increase of heat shock protein 70(72) in the EBZ of bortezomib-treated animals compared with control. There was a striking absence of rapid (>300 beats/min) and very rapid (>360 beats/min) ventricular triplets that is highly predictive of sudden cardiac deaths (SCDs) during electrocardiogram monitoring of the first 24 h in the bortezomib-treated animals in contrast with nontreated infarcted animals. There were no SCDs in the 6 treated animals (0%) and five SCDs in the 14 control animals (36%). Assay of whole blood proteasome activity demonstrated the expected decrease over the 24-h observation period. These data support the concept that proteasome inhibition within a window of time following myocardial infarction may be of use in suppressing malignant tachyarrhythmias and SCD.     

Influence of pregnancy on mean systemic filling pressure and the cardiac function curve in guinea pigs.

To assess the degree of circulatory fullness and to evaluate the influence of peripheral and cardiac factors in the regulation of cardiac output during pregnancy, the following studies were conducted using pentobarbital-anesthetized, open-chest nonpregnant and late term pregnant guinea pigs. Mean circulatory filling pressure was taken as the equilibrium pressure when the pulmonary artery was constricted. Total vascular compliance was assessed by +/- 5-mL changes in blood volume performed while this constriction was maintained. A separate group of guinea pigs was prepared with a pulmonary artery electromagnetic flow probe and right atrial catheter. Rapid infusion of saline was used to increase right atrial pressure while the cardiac output was determined. Pregnancy was characterized by the following changes relative to nonpregnant controls: 51Cr-labelled RBC blood volume increased from 55 +/- 3 to 67 +/- 3 mL/kg; mean circulatory filling pressure increased from 7.1 +/- 0.2 to 8.0 +/- 0.5 mmHg (1 mmHg = 133.322 Pa); right atrial pressure decreased from 3.4 +/- 0.2 to 2.1 +/- 0.3 mmHg; and cardiac output increased from 71.8 +/- 3.9 to 96.8 +/- 3.3 mL.min-1.kg-1. Total vascular compliance was not changed (2.1 +/- 0.1 mL.kg-1.mmHg-1) and most of the expanded blood volume was accommodated as unstressed volume. The cardiac function curve was shifted upwards in pregnant animals. The resistance to venous return, as determined from the slope of the venous return curves, was not changed. These data suggest that the circulation of the pregnant guinea pig is slightly overfilled.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bronchovascular responses to intravenous contrast media for helical CT pulmonary angiography

CT angiography is now commonly used for the diagnosis of pulmonary embolism, but the contrast media used for imaging produces various hemodynamic changes. In this study, we investigated the bronchovascular and hemodynamic responses to intravenous iopromide, a non-ionic contrast agent used for pulmonary CT angiograms, in anesthetized, mechanically ventilated sheep (n = 6). Bronchial blood flow and cardiac output were measured with ultrasonic flow probes. Systemic and pulmonary arterial pressures were continuously monitored. Injections of 0.9% NaCl (120 ml over 30 s) or iopromide (300 mg/ml, 120 ml over 30 s) were given in random order in a peripheral vein with an angiogram infuser and hemodynamic changes were determined. After these parameters returned to baseline, the left pulmonary artery (LPA) was occluded with a snare and the animals were allowed to stabilize. Injections of NaCl and iopromide were repeated in random order as before. There were no significant hemodynamic effects with infusion of NaCl. With intact pulmonary vasculature, NaCl and iopromide did not cause significant changes in arterial blood gases, however, cardiac output (QT, L/min), mean systemic and pulmonary arterial pressures (PSA and PPA, Torr) increased and bronchovascular resistance (BVR, Torr x min/ml), decreased. Following LPA ligation, pH and PO2 significantly decreased over baseline, whereas PCO2 increased. After LPA ligation, iopromide produced a greater decrease in BVR as compared with preligation intact pulmonary vasculature. In conclusion, iopromide caused rapid hemodynamic changes and decreased BVR, likely secondary to osmolar stress. Bronchovascular effects were more pronounced after pulmonary arterial occlusion.     

The role of the cardiac-pulmonary blood volume in the changes in left ventricle output during stimulation of the afferent fibers of somatic nerves

Stimulation of tibial nerve afferent fibers has revealed heterogeneous shifts of left ventricular output, as well as pulmonary artery and posterior vena cava blood flow in anesthetized cats. Uniform changes in left ventricular output and pulmonary artery blood flow were noted in the majority of cases, with venous return most often exceeding pulmonary artery blood flow. beta-adrenoreceptor blockade failed to influence changes in pulmonary artery blood flow. It is concluded that the increase in pulmonary artery blood flow depends on the rise in venous return, but not on neurogenic influence upon the right ventricle. The reduction in left ventricular output is the result of decreased right ventricular outflow due to its overload caused by pulmonary vasoconstriction.     

Furosemide reduces lung fluid filtration in lambs with lung microvascular injury from air emboli

To study the effects of furosemide on the neonatal pulmonary circulation in the presence of lung injury, we measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, and concentrations of protein in lymph and plasma of nine lambs that received furosemide, 2 mg/kg iv, during a continuous 8-h intravenous infusion of air. Air embolism increased pulmonary vascular resistance by 71% and nearly tripled steady-state lung lymph flow, with no change in lymph-to-plasma protein ratio. These findings reflect an increase in lung vascular protein permeability. During sustained lung endothelial injury, diuresis from furosemide led to a rapid reduction in cardiac output (average 29%) and a 2-Torr decrease in left atrial pressure. Diuresis also led to hemoconcentration, with a 15% increase in both plasma and lymph protein concentrations. These changes were associated with a 27% reduction in lung lymph flow. In a second set of studies, we prevented the reduction in left atrial pressure after furosemide by inflating a balloon catheter in the left atrium. Nevertheless, lymph flow decreased by 25%, commensurate with the reduction in cardiac output that occurred after furosemide. In a third series of experiments, we minimized the furosemide-related decrease in cardiac output by opening an external fistula between the carotid artery and jugular vein immediately after injection of furosemide. In these studies, the reduction in lung lymph flow (average 17%) paralleled the smaller (17%) decrease in cardiac output. These results suggest that changes in lung vascular filtration pressure probably do not account for the reduction in lung lymph flow after furosemide in the presence of lung vascular injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

External transport of beta-adrenergic binding sites in ischemic myocardium

The properties of beta-adrenergic receptors were studied in normal and in flow restricted regions of the dog heart. Purified cardiac membrane preparations and papillary muscle preparations were isolated from control and ischemic areas and tested a) following chronic beta-receptor blockade with metipranolol or exaprolol, and b) after acute regional myocardial ischemia. A significant reduction in the sensitivity of the heart muscle preparations from compromised heart for isoprenaline resulting in a reduced affinity of beta-adrenergic receptors to exaprolol was observed. Quantitative ligand binding data showed higher numbers of (3H) dihydroalprenolol/(3H) DHA/binding sites in the membrane fraction obtained from compromised compared to control myocardium. The ratio of intra- to extracellular beta-adrenergic receptors decreased from 1.35 to 0.55 in the membrane fractions obtained from the compromised hearts. Pretreatment of experimental animals with metipranolol or propranolol attenuated the observed increase in the total number of beta-adrenergic receptor sites in myocardial membrane fractions from ischemic hearts. These data suggest preferential distribution of beta-adrenergic binding sites from intracellular to membrane fractions in flow restricted regions of the dog heart after coronary occlusion.     

Hemodynamic mechanisms of the pulmonary artery pressure and blood flow changes following vasoactive depressor drugs injection

The character and values of changes of the pulmonary hemodynamics and venous return following acetylcholine, histamine and isoproterenol intravenous injection were studied in acute experiments on the anesthetized cats. After depressor drugs injection the character and values of changes of pulmonary artery pressure and flow were different. In 67% cases the pulmonary artery pressure was decreased, and in 33%--it was elevated, meanwhile the pulmonary artery flow was decreased in 48% cases and it was increased in 52%, i.e., in the equal number of observations. Thus, following depressor drugs intravenous injection, hemodynamic mechanisms of the changes of pulmonary artery pressure and flow are different. The character and values of changes of the pulmonary artery pressure are correlated with the changes of pulmonary vascular resistance and are not dependent with the left atrial pressure shifts. The changes of the pulmonary artery blood flow are caused by the changes of the venous return and are not correlated with the changes of the right and left atrial pressure.     

Pressor and vascular responsiveness in renal prehypertensive rabbits with a nonfiltering kidney

This study examined the possibility that the renal tubules are the site of the sensors that respond to renal artery stenosis (RAS) and which initiate the events leading to pressor hyperresponsiveness. A nonfiltering kidney (NFK) was produced in 32 rabbits by 2 hr of total renal ischemia plus permanent ligation of the ureter; the opposite kidney remained undisturbed. Sixteen of these rabbits also received RAS of the NFK. An additional 16 rabbits received RAS without production of a NFK, and 16 more rabbits were sham-operated controls. In acute experiments 3 days later in conscious rabbits, infusions of norepinephrine at several doses resulted in greater increases in mean arterial pressure in the RAS rabbits, with filtering kidneys (2-K, 1-clip) and with NFKs (2-K, 1-clip with NFK), than in the NFK rabbits without RAS (2-K control with NFK) or in the control rabbits (2-K control). Measurements of cardiac output revealed greater increases in total peripheral resistance as well as in mean arterial pressure in response to norepinephrine in the RAS rabbits both without and with a NFK. Because production of a NFK in rabbits did not prevent the development of pressor and vascular hyperresponsiveness 3 days after RAS, these studies indicated that the renal sensors that detect changes in the kidney following RAS and which initiate the series of events leading to pressor and vascular hyperresponsiveness, probably are not located in the renal tubules.     

Myocardial ischemia-mediated excitatory reflexes: a new function for thromboxane A2?

Clinical and experimental evidence has shown that myocardial ischemia activates cardiac spinal afferents that mediate sympathoexcitatory reflex responses. During myocardial ischemia, thromboxane A2 (TxA2) is released in large quantities by activated platelets in the coronary circulation of patients with coronary artery disease. We hypothesized that endogenous TxA2 contributes to sympathoexcitatory reflexes during myocardial ischemia through stimulation of TxA2/prostaglandin endoperoxide (TP) receptors. Regional myocardial ischemia was induced by occlusion of a diagonal branch of left anterior descending coronary artery of anesthetized cats. Hemodynamic parameters and renal sympathetic nerve activity were recorded after sinoaortic denervation and bilateral vagotomy. Regional myocardial ischemia evoked significant increases in mean blood pressure (122+/-10 vs. 139+/-12 mmHg, before vs. ischemia), aortic flow (153+/-18 vs. 167+/-20 ml/min), first derivative of left ventricular pressure at 40-mmHg developed pressure (2,736+/-252 vs. 2,926+/-281 mmHg/s), systemic vascular resistance (0.6+/-0.1 vs. 0.9+/-0.12 peripheral resistance units), and renal sympathetic nerve activity (by 22%). The reflex nature of the excitatory responses was confirmed by observing its disappearance after blockade of cardiac nerve transmission with intrapericardial 2% procaine treatment. Moreover, application of U-46619 (2.5-10 microg), a TxA2 mimetic, on the heart caused graded increases in mean arterial pressure and renal nerve activity, responses that were abolished 3 min after local blockade of cardiac neural transmission with intrapericardial procaine. BM 13,177 (30 mg/kg iv), a selective TP receptor antagonist, eliminated the reflex responses to U-46619 and significantly attenuated the excitatory responses during brief (5 min) regional myocardial ischemia. The sympathoexcitatory reflex responses to U-46619 were unchanged by blockade of histamine H1 receptors with pyrilamine and serotonin 5-HT3 receptors with tropisetron, indicating specificity of this TP receptor agonist. These data indicate that endogenous TxA2 participates in myocardial ischemia-mediated sympathoexcitatory reflex responses through a TP receptor mechanism.     

Alpha-adrenergic tone in the coronary circulation of the conscious dog

To examine the role of neural factors in the control of coronary vasoactivity in conscious animals, dogs were supplied with miniature pressure gauges in the aorta and left ventricle (to measure aortic and left ventricular pressures, respectively and with a flow probe on the left circumflex coronary artery (to measure coronary blood flow). The experiments were conducted several weeks after recovery from operation. Stimulation of the carotid chemoreceptor and pulmonary inflation elicited a biphasic reflex response. Initially, coronary vasodilation was observed; coronary blood flow tripled even after changes in metabolic factors were minimized by pretreatment with propranolol. A similar response occurred after a spontaneous deep breath. The coronary vasodilation could be blocked by alpha-adrenergic receptor blockade. The second phase of the response involved an increase in coronary vascular resistance, associated with elevated arterial pressure and an absolute reduction in coronary blood flow and coronary sinus oxygen content. The secondary coronary vasoconstriction was also abolished by alpha-adrenergic blockade. Paradoxically, alpha-adrenergic receptor blockade with phentolamine (at constant heart rate and after beta-adrenergic receptor blockade) did not increase coronary blood flow and reduced coronary vascular resistance only slightly. Selective alpha 1-adrenergic receptor blockade with prazosin and trimazosin on different days induced progressively greater reductions in coronary vascular resistance. Trimazosin was the only alpha-adrenergic receptor blocker to elevate coronary blood flow significantly. It is conceivable, but speculative, that withdrawal of alpha-adrenergic tone may involve activation of an intermediate agent, which is a potent coronary vasodilator. Alternatively, withdrawal of alpha-adrenergic tone may be an important mechanism for immediate control of the coronary circulation, but under more chronic conditions it plays a lesser role as a result of suppression by metabolic factors.     

Recent Advances in Hypertension

The possible relationship between the renal mechanism of volume control and blood pressure regulation is discussed. Expansion of the extracellular fluid (ECF) and plasma volumes was demonstrated following renal artery constriction in the rat; after about one month ECF volume returned to normal although hypertension persisted. Measurements of cardiac output in the unanesthetized rat by an implanted electromagnetic flowmeter showed an initial rise in cardiac output after renal artery constriction, returning to normal in 10 to 15 days. A homeostatic hypothesis for the production of renal hypertension is put forward in which changes in ECF volume, capacity vessel tone and myocardial contractility participate in the development of hypertension by elevating cardiac output. Autoregulation of peripheral flow then occurs and the consequent restoration of blood pressure at a renal pressure receptor results in return to normal of cardiac output by negative feedback. Thus in chronic hypertension the high peripheral resistance is maintained by autoregulation.     

Hemodynamics mechanisms of changes in the right atrial pressure following intravenous injection of the depressor drugs

Changes of the right atrial pressure, superior and inferior vena cava flows, right ventricular myocardial contractility (first derivate of right ventricular pressure, dP/dt max) following i.v. injection of acetylcholine, histamine and isoproterenol, were studied in acute experiments on anaesthetized mongrel cats with artificial lung ventilation and opened chest. The right atrial pressure in those cases could be increased (I group of animals) or decreased (II group). In maximal shifts of right atrial pressure following acetylcholine injection, the superior vena cava flow increased but the inferior vena cava flow decreased in equal proportion. When the right ventricular myocardial contractility decreased more than the right atrial pressure was augmented, and when the cardiac negative inotropic effect was weak, the right atrial pressure was reduced. After histamine injection in both groups of animals, right ventricular myocardial contractility was increased on the same level, and changes of the inferior vena cava flow were insignificant. The right atrial pressure was elevated following greater increase of superior vena cava flow. Isoproterenol caused the positive cardiac inotropic effect and augmenting of the superior vena cava flow in both groups of animals. The right atrial pressure was elevated if the inferior vena cava flow increased and, on the other hand, when the inferior vena cava flow decreased the right atrial pressure was reduced. Thus different maximal changes of the right atrial pressure following i.v. injection of acetylcholine, histamine and isoproterenol could be explained by different hemodynamic mechanisms of the interaction between superior and inferior vena cava flow shifts and changes of the right ventricular myocardial contractility.     

Circulatory effects of prolonged hypoxia before and during antihistamine.

Five chronically instrumented healthy dogs were exposed to a 5-day period of breathing 10% oxygen in a chamber. The response to hypoxia was found to be time dependent. During the first 24 h of hypoxia the circulatory response was characterized by increases in cardiac output, heart rate, pulmonary and systemic arterial blood pressures, and pulmonary vascular resistance. Systemic vascular resistance increased; left atrial pressure decreased. During the early part of hypoxia the animals became hypocapnic; the arterial blood pH rose significantly. During the rest of the hypoxic period cardiac output, heart rate, and arterial blood pH returned to the control values; pulmonary and systemic arterial pressures and pulmonary vascular resistance remained significantly elevated. Systemic vascular resistance rose; left atrial pressure remained below control. This response to hypoxia was not substantially modified when the experiment was repeated during the administration of the antihistamine promethazine, an H1-receptor blocking agent, in a dose which blocked the pulmonary vasoconstrictor response to small doses of exogenous histamine. The circulatory response to acute hypoxia in five anesthetized dogs was not modified by intravenous administration of metiamide, an H2-receptor blocking agent.     

结扎冠状动脉后快速起搏方法建立急性心功能不全动物模型

目的探讨建立急性心功能不全动物模型的可行性。方法完全结扎犬前降支,进行快速右室起搏,使心输出量(CCO)较基础状态稳定地下降50%,分别测定基础及心输出量下降状态下的血压(AP)、血氧(SaO2)、平均右房压(mRAP)、平均肺毛压(mPCWP)、系统血管阻力(SVR)、心腔大小、左室射血分数(LVEF)、血浆肾素活性(PRA)、内皮素(ET)、尿量(UO)、血肌酐(Scr)、肌酐清除率(Ccr)。结果结扎LAD和快速右室起搏后,CCO较基础状态均稳定地下降50%,CCO降低后,AP、SaO2显著下降,mRAP、mPCWP、SVR显著升高;心脏各腔室明显扩大,LVEF显著降低;PRA、ET、Scr明显升高,UO、Ccr明显下降。结论结扎冠状动脉前降支及快速右心室起搏可成功制作急性心功能不全的动物模型。     

Influence of vasoactive intestinal polypeptide (VIP) on splanchnic and central hemodynamics in healthy subjects

The influence of VIP, a potent vasodilator, on central hemodynamics, splanchnic blood flow and glucose metabolism was studied in six healthy subjects. Teflon catheters were inserted into an artery, a femoral vein and a right-sided hepatic vein. A Swan-Ganz catheter was introduced percutaneously and its tip placed in the pulmonary artery. Determinations of cardiac output, systemic, pulmonary arterial and hepatic venous pressures as well as splanchnic blood flow were made in the basal state and at the end of two consecutive 45 min periods of VIP infusion at 5 and 10 ng/kg/min, respectively. Arterial blood samples for analysis of glucose, FFA, insulin and glucagon were drawn at timed intervals. VIP infusion at 5 ng/kg/min resulted in an increase in cardiac output (55%) and heart rate (25%) as well as a reduction in mean systemic arterial pressure (15%) and vascular resistance (45%). With the higher rate of VIP infusion heart rate tended to rise further while cardiac output and arterial pressure remained unchanged. At 15 min after the end of VIP infusion the above variables had returned to basal levels. Splanchnic blood flow and free hepatic venous pressure did not change significantly. Arterial concentrations of glucose, FFA, insulin and glucagon increased during VIP infusion. At 15 min after the end of infusion the glucose levels were still significantly higher than basal (20%). Net splanchnic glucose output did not change in response to VIP infusion. It is concluded that VIP exerts a potent vasodilatory effect resulting in augmented cardiac output and lowered systemic blood pressure and vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)