The effects of insulin on mesenteric blood flow in anaesthetized pigs

Infusion of insulin in anaesthetized pigs has been shown to cause an increase in renal blood flow and a decrease in coronary blood flow, which were the net result of a vasoconstriction involving sympathetic alpha-adrenoceptor-mediated mechanisms and of a local vasodilatation involving the endothelial release of nitric oxide. In the present study, the effect of insulin on superior mesenteric blood flow was examined in pentobarbitone-anaesthetized pigs at constant heart rate, aortic blood pressure, left ventricular contractility and blood levels of glucose and potassium. In 10 pigs, infusion of 0.004 IU kg(-1) min(-1) of insulin increased mesenteric flow. In five of these pigs, intravenous phentolamine enhanced the increase in mesenteric flow elicited by insulin, a response which was abolished by the subsequent injection of N(omega)-nitro-L-arginine methyl ester (L-NAME) into the mesenteric artery. In the remaining five pigs, infusion of insulin after intramesenteric injection of L-NAME caused a decrease in mesenteric flow. This response was abolished by the subsequent intravenous administration of phentolamine. The present study showed that infusion of insulin in anaesthetized pigs primarily caused a mesenteric vasodilatation, which was the net result of two opposite effects, namely a predominant vasodilatation mediated by the endothelial release of nitric oxide and a sympathetic vasoconstrictor mechanism mediated by alpha-adrenoceptors.     

The role of nitric oxide in the coronary vasoconstriction caused by growth hormone in anaesthetized pigs

Intravenous injection of growth hormone in anaesthetized pigs has been shown to cause coronary vasoconstriction by antagonizing the vasodilatory effects of 2-adrenergic receptors. Because nitric oxide is believed to modulate or mediate 2-adrenergic effects, the present study was undertaken in the same experimental model to determine the role of nitric oxide in the above response to growth hormone. In fourteen pigs anaesthetized with sodium pentobarbitone, changes in left circumflex or anterior descending coronary blood flow caused by intravenous injection of 0.05 i.u. kg-1 of growth hormone at constant heart rate and arterial blood pressure were assessed using electromagnetic flowmeters. In a first control group of six pigs, growth hormone caused a decrease in coronary blood flow which averaged 13.1 % of the baseline values. In a second group of eight pigs, intravenous administration of N-nitro-L-arginine methyl ester (L-NAME) was used to block the endothelial release of nitric oxide. In these pigs, the subsequent injection of growth hormone did not cause any significant changes in coronary blood flow, even when performed after reversing the increase in arterial blood pressure and coronary vascular resistance caused by L-NAME with continuous intravenous infusion of papaverine. These results indicated that the coronary vasoconstricting effect of growth hormone, known to involve antagonism of 2-adrenergic vasodilatory effect, was mediated by inhibition of nitric oxide release.     

The role of nitric oxide in the peripheral vasoconstriction caused by human placental lactogen in anaesthetized pigs

Regional intra-arterial infusion of human placental lactogen in anaesthetized pigs has been shown to cause coronary, renal and iliac vasoconstriction by antagonizing the vasodilatory effects of beta2-adrenergic receptors. Since nitric oxide is known to modulate or mediate beta2-adrenergic effects, the present study was planned in the same experimental model to determine the role of nitric oxide in the above vascular responses to human placental lactogen. In eight pigs anaesthetized with sodium pentobarbitone, changes in anterior descending coronary, left renal and left internal iliac blood flow caused by intra-arterial infusion of human placental lactogen at constant heart rate and arterial blood pressure were assessed using electromagnetic flowmeters. Intra-arterial infusion of the human placental lactogen caused decreases in coronary, renal and iliac blood flow which, respectively, averaged 16.7, 8.1 and 12.2% of the baseline values. The role of nitric oxide in this response was studied in the same pigs by repeating the experiments, after measured blood flows had returned to baseline values, following intra-arterial administration of N(omega)-nitro-L-arginine methyl ester (L-NAME). The subsequent intra-arterial infusion of human placental lactogen did not cause any significant changes in measured blood flows, even when performed after reversing the increase in arterial blood pressure and coronary, renal and iliac resistance caused by L-NAME with continuous intravenous infusion of papaverine. These results indicate that the coronary, renal and iliac vasoconstriction caused by human placental lactogen, known to involve antagonism of beta2-adrenergic vasodilatory effects, was mediated by inhibition of nitric oxide release.     

The primary reflex effects of distension of the stomach on heart rate,arterial pressure and left ventricular contractility in the anaesthetized pig

The present study was planned to investigate whether distension of the stomach primarily affects the heart rate, arterial blood pressure and left ventricular inotropic state and to explore the reflex mechanisms involved. In 16 anaesthetized pigs, distension of gastric balloons with 0.8 1 of Ringer solution (gastric transmural pressure of about 13 mmHg) without controlling any haemodynamic variable caused an increase in arterial blood pressure. When this response was prevented, an increase in heart rate was obtained in each animal. In five pigs, the increase in heart rate was graded by step increments of distension. No significant changes in maximum rate of change of left ventricular pressure were observed in the sixteen pigs during gastric distensions performed whilst preventing changes in heart rate and arterial blood pressure. The responses of arterial blood pressure and heart rate were not influenced by the administration of atropine (four and six pigs respectively), while they were abolished by the administration of bretylium tosylate (ten pigs) and by bilateral vagotomy (six pigs; three cervical, three subdiaphragmatic). The present study showed that gastric distension which was likely to be innocuous in the anaesthetized pig reflexly increased arterial blood pressure and heart rate. The afferent limb of the reflex was in the vagal nerves and the efferent limb involved sympathetic pathways.     

Minimal effects of nitric oxide on spatial blood flow heterogeneity of the dog heart

 Eleven Beagle dogs were studied to elucidate the possible role of L-arginine-derived nitric oxide on local blood flow distribution in left and right ventricular myocardium. Local blood flow was determined in 256 samples from the left and 64 samples from the right ventricle per heart using the tracer microsphere technique (mean sample mass 319 ± 131 mg). Nitric oxide production was effectively inhibited by intravenous infusion of 20 mg/kg nitro-L-arginine methylester (L-NAME) as evidenced by a shift of the dose/response curve for the effect of intracoronary administration of bradykinin (0.004–4.0 nmol/min) on coronary blood flow. L-NAME enhanced left and right ventricular systolic pressures from 132 ± 18 to 155 ± 15 mm Hg and from 26 ± 3 to 29 ± 3 mm Hg respectively (both P = 0.043). Mean left ventricular blood flow was 1.14 ± 0.38 before and 0.99 ± 0.28 ml min^–1 g^–1 after L-NAME (P = 0.068), while right ventricular blood flow fell from 0.72 ± 0.28 to 0.53 ± 0.20 ml min^–1 g^–1 (P = 0.043). Coronary conductance of left and right ventricular myocardium fell by 31 and 43% respectively (both P = 0.043). The coefficient of variation of left ventricular blood flow was 0.26 ± 0.07 before and 0.29 ± 0.07 after L-NAME (P = 0.068), that of right ventricular blood flow was 0.27 before and after L-NAME. Skewness (0.51) and kurtosis (4.23) of left ventricular blood flow distribution were unchanged after L-NAME, while in the right ventricle skewness decreased from 0.54 to 0.09 (P = 0.043) and kurtosis (3.68) tended to decrease after L-NAME (P = 0.080). The fractal dimension (D = 1.20–1.27) and the corresponding nearest-neighbor correlation coefficient (r _n = 0.37–0.53) of left and right ventricular myocardium remained unchanged after infusion of L-NAME. From these results it is concluded that firstly, local nitric oxide release does not explain the higher perfusion of physiological high flow samples and secondly, that spatial myocardial blood flow coordination is not dependent on nitric oxide. Received: 11 July 1996 / Received after revision: 29 October 1996 / Accepted: 17 December 1996     

Calcium-induced net potassium uptake of pig hearts in vivo.

To determine whether the catecholamine-induced myocardial potassium uptake could be mimicked by increasing extracellular and intracellular calcium concentrations in vivo, we measured changes in myocardial potassium balance in nine anaesthetized open-chest pigs with PVC-valinomycin electrodes in arterial and coronary sinus blood. CaCl2 infusion (200-400 mumol min-1) into the left coronary artery increased coronary sinus blood calcium concentration from 2.29 (2.19-2.42) to 4.63 (3.76-5.67) mmol l-1 (median, 95% confidence interval, P = 0.01) indicating a similar increment in myocardial extracellular calcium concentration. The contractility measure LV dP/dt increased 95 (76-147) %, indicating a substantial increment in intracellular calcium concentration. During the CaCl2 infusion coronary sinus potassium concentration declined to a nadir 0.12 (0.09-0.17) mmol l-1 below baseline (P = 0.008) whereas arterial concentration remained unchanged. Peak myocardial potassium uptake was 18 (7-32) mumol min-1 100 g-1 and occurred 150 (110-195) s after start of infusion. The response remained unaltered after adrenoceptor blockade by prazosin and propranolol. Prolonged CaCl2 infusion caused a net myocardial potassium loss which was accompanied by metabolic and haemodynamic indications of myocardial ischaemia. These findings are consistent with enhanced Na-K pump activity in the intact beating pig heart in response to increased extracellular and intracellular calcium concentrations.     

Mechanism of cardiac output response to hypertonic sodium chloride infusion in dogs.

Hypertonic sodium chloride and tris(hydroxymethyl)amino-methane (Tris) hydrochloride (0.3 mmol/kg.min) were infused intravenously into chloralose-anesthetized dogs over a 20-min period. Cardiac output, maximum left ventricular dP/dt, and (dP/dt)/P increased by 55, 33, and 23%, respectively, during NaCl infusion, but Tris HCl infusion had no effects. NaCl infusion did not change heart rate or left ventricular end-diastolic pressure. Mean systemic and pulmonry arterial blood pressures increased, whereas total peripheral and pulmonary vascular resistances decreased. Responsiveness of cardiac beta-adrenergic receptors, as determined by serial intravenous injections of epinephrine, was not affected by NaCl infusion. Plasma catecholamine concentration, however, increased during NaCl infusion. In addition, the increases in cardiac output, maximum left ventricular dP/dt and (dP/dt)/P were abolished by prior treatment with practolol, a cardioselective beta-adrenergic receptor blocking agent. These results suggest that the hemodynamic effects of NaCl infusion were caused, at least in part, by the inotropic action of catecholamines.     

The effect of distension of the stomach on coronary blood flow in anaesthetized pigs

The present study was undertaken in anaesthetized pigs to determine whether distension of the stomach reflexly affects coronary blood flow. Experiments were performed on 17 pigs anaesthetized with ketamine and sodium pentobarbitone and artificially ventilated. Coronary blood flow was measured with an electromagnetic flowmeter positioned around the origin of the left circumflex coronary artery. The stomach was distended by injecting 0.81 warm Ringer solution into a balloon positioned within the stomach (mean gastric transmural pressure of about 13 mm Hg). Changes in aortic blood pressure and heart rate were prevented by a pressurized reservoir connected to the left femoral artery and by atrial pacing respectively. Distension of the stomach always caused a decrease in mean coronary blood flow. In five pigs, the magnitude of the decrease in coronary blood flow was graded by step increments in the gastric distending volume from 0.6 l to 1 l. The response of coronary blood flow was not affected by the administration of atropine (12 pigs), while it was abolished by the administration of bretylium tosylate (eight pigs) and by bilateral vagotomy (eight pigs; four cervical, four subdiaphragmatic vagotomy). These results show that innocuous distension of the stomach in anaesthetized pigs reflexly decreases coronary blood flow. This reflex response is mediated by sympathetic effects and its afferent limb involves the vagal nerves.     

Sleep-induced hypotension precipitates severe myocardial ischemia

STUDY OBJECTIVES: Epidemiologic studies have shown a high frequency of major cardiac events at night in patients with coronary artery disease. This has been attributed to the sympathetic surges accompanying rapid eye movement (REM) sleep; the role of non-REM sleep, which comprises 80% of total sleep duration, has been largely neglected. Accordingly, we evaluated the effect of non-REM sleep on contractile function in a region of the left ventricular wall supplied by a flow-limiting coronary stenosis. DESIGN: Eight domestic pigs were chronically instrumented to measure regional left ventricular contractile function (wall thickening), coronary blood flow, and systemic hemodynamic variables. Measurements were obtained: (1) during wakefulness, i.e., conscious condition, prior to imposition of coronary stenosis; (2) during wakefulness following imposition of coronary stenosis (30% reduction of baseline coronary blood flow from 40 +/- 4 to 27 +/- 3 mL/min); and (3) during non-REM sleep with coronary stenosis maintained. RESULTS: During wakefulness, coronary stenosis reduced wall thickening (from 23.3 +/- 3.4% to 15.7 +/- 2.0%), whereas mean arterial pressure and heart rate were unchanged. With coronary stenosis maintained, the onset of non-REM sleep caused 20% decreases in mean arterial pressure and coronary blood flow, accompanied by a cessation of regional wall thickening, i.e., akinesis (wall thickening = 0.2 +/- 2.8%), indicating severe myocardial ischemia. CONCLUSIONS: The arterial hypotension, and associated reduction in coronary blood flow, during non-REM sleep precipitated severe myocardial ischemia in a region of the left ventricular wall supplied by flow-limiting coronary stenosis. Such episodes would occur repeatedly during the sleep cycle and could potentially set the stage for a major cardiac event during the sympathetic activation accompanying REM sleep or morning activities.     

Reflex vascular responses to changes in left ventricular pressures, heart rate and inotropic state in dogs.

Dogs were anaesthetized with chloralose, artificially ventilated and the chests widely opened. Left ventricular mechanoreceptors, including those in or near the coronary arteries, were stimulated by changing the pressure in the aortic root. The pressures distending the left atrium and the aortic and carotid baroreceptors were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a hind limb and to the rest of the systemic circulation, which were perfused independently at constant flows. Physiological increases in peak left ventricular and coronary arterial pressures resulted in vasodilatation in both regions. These responses were not influenced by changes in the heart rate. Stimulation of the left cardiac sympathetic nerves resulted in increases in peak ventricular pressure and in the maximal rate of change of pressure (dP/dtmax). This also resulted in increases in perfusion pressures (vasoconstriction) at all levels of peak ventricular pressure although there was little effect on the responses to changes in ventricular pressure. Sympathetic stimulation had little effect on the relationship between perfusion pressures and aortic root pressure. Increases in ventricular filling also resulted in vasoconstriction at all levels of peak ventricular pressure. Increases in filling, however, did not affect the relationship between either perfusion pressure and aortic root pressure. Conversely, decreases in left ventricular filling, by bypassing some of the left atrial blood, resulted in vasodilatation at all levels of peak ventricular pressures but had no effect on the perfusion pressures at any aortic root pressure. The combination of sympathetic stimulation with decreased ventricular filling resulted in little effect on perfusion pressures or on their responses to changes in either aortic root or ventricular systolic pressures. We conclude that the vascular responses to stimulation of left ventricular mechanoreceptors are not enhanced by sympathetic stimulation, decreases in ventricular filling or the combination of the two. The apparent effects of each of these interventions alone on the relationships between perfusion pressures and ventricular, but not aortic root, pressure, could be explained if the receptors responsible were sensitive more to changes in aortic root and coronary arterial pressures than to pressure changes in the ventricle itself.     

Coronary flow and left ventricular pressure during diastole in the anaesthetized dog.

There is controversy about the effect of left ventricular pressure on resistance of the intramyocardial coronary vessels. In anaesthetized dogs the effect of left ventricular pressure on coronary flow during diastole was studied using an extracorporeal circulation and allowing the heart to contract and relax isovolumically. At constant coronary perfusion pressure of about 45 mmHg with maximal coronary vasodilatation, produced by dipyridamole, increases in diastolic left ventricular pressure to 22 mmHg, producing a volume of 50 ml, did not affect diastolic coronary flow. It is suggested that in the intact animal over the physiological range of left ventricular diastolic pressure the resistance in the coronary vessels is not affected.     

Endothelial dysfunction in rat mesenteric artery after regional cardiac ischaemia-reperfusion

In most previous studies, ischaemia-reperfusion (I/R)-induced vascular injury referred to injury in the tissue or blood vessel that was directly subjected to I/R. However, less attention has been focused on remote vascular injury that might be caused by cardiac I/R. In the present study, we aimed to assess whether cardiac I/R could affect vasoconstriction and vasodilatation in mesenteric arteries from Sprague-Dawley rats. Left anterior descending coronary arteries from adult male Sprague-Dawley rats were occluded (60 min) and then reperfused (120 min). Changes in haemodynamic parameters indicated that this procedure caused evident cardiac dysfunction. In mesenteric arteries isolated from the animals, cardiac I/R significantly increased the maximal contractions in response to KCl, 5-hydroxytryptamine, phenylephrine and U46619 and decreased the maximal relaxation in response to acetylcholine, but not to sodium nitroprusside, compared with sham-operated animals. The nitric oxide synthase inhibitor L-NAME abolished differences of contractile responses to phenylephrine between sham-operated and I/R rats. The antioxidant N-acetyl-L-cysteine reversed the impairment of acetylcholine-stimulated vasodilatation induced by regional cardiac I/R. However, L-NAME caused a similar degree of inhibition of acetylcholine-stimulated relaxation in mesenteric arteries from sham-operated and I/R rats. Electron microscopy revealed that mesenteric arterial endothelial structure was degraded in the I/R group and that N-acetyl-L-cysteine treatment prevented this structural damage. In conclusion, regional cardiac I/R caused by transient occlusion and reperfusion of the left anterior descending coronary artery results in peripheral vascular endothelial dysfunction.     

Effects of ranitidine and cimetidine on experimentally induced ventricular arrhythmias in anaesthetized rats

The effects of two histamine H₂-receptor antagonists, ramitidine and cimetidine, on ventricular arrhythmias induced by acute coronary artery ligation and by aconitine infusion were studied in pentobarbitone-anaesthetized rats. The changes in arterial blood pressure and heart rate were also observed. It was found that both drugs significantly reduced the incidence, and prolonged the time of onset, of ventricular tachycardia and ventricular fibrillation following acute coronary artery ligation; however, they did not significantly alter the incidence or time of onset of ventricular dysrhythmias caused by aconitine infusion. These findings further support the hypothesis that histamine release may contribute to the genesis of early ventricular arrhythmias resulting from acute myocardial ischaemia. Since the decreased blood pressure induced by coronary artery ligation was not significantly prevented by pretreatment with either histamine H₂-receptor blocker, this suggests that histamine may not be responsible for the blood pressure changes during acute myocardial ischaemia.     

Haemodynamic effects of the intravenous administration of growth hormone in anaesthetized pigs

 Administration of growth hormone in humans has been reported variably to affect arterial blood pressure and ventricular contractility. The present study was undertaken in anaesthetized pigs to establish whether increases in the blood levels of growth hormone primarily affect haemodynamic variables and to determine the mechanisms involved. In pigs anaesthetized with pentobarbitone sodium, left circumflex or anterior descending coronary blood flow was measured with an electromagnetic flowmeter. In a first group of 23 pigs, growth hormone administration (0.05 IU kg^–1 i.v.) increased aortic blood pressure and reduced coronary blood flow when heart rate and aortic blood pressure were held constant. These responses were augmented by graded increases in plasma levels of growth hormone. The mechanisms of the above responses were studied in a second group of 29 pigs and involved β₂-adrenergic receptors since they were abolished by propranolol or butoxamine but not by atropine, phentolamine or atenolol . The present study showed that administration of growth hormone in anaesthetized pigs primarily increased aortic blood pressure and vasoconstricted the coronary circulation. The mechanisms of these responses involved β₂-adrenoceptor effects. Received: 16 October 1997 / Received after revision: 12 December 1997 / Accepted: 26 February 1998     

Nitric oxide requirement for vasomotor nerve-induced vasodilatation and modulation of resting blood flow in muscle microcirculation

Intravital microscopy of rabbit tenuissimus muscle was used for studies of endogenous nitric oxide as a microvascular regulator in vivo. Derivatives of arginine were administered in order to modulate the formation of nitric oxide from L-arginine. N omega-nitro-L-arginine methylester (L-NAME) (1-100 mg kg-1 i.v.) dose-dependently reduced microvascular diameters. A concomitant blood pressure increase and a decrease in heart rate was observed. The blood pressure increase induced by L-NAME (30 mg kg-1) was reversed by L-arginine (1 g kg-1) but not D-arginine. Vasodilation in response to topical acetylcholine (0.03-3 microM) was significantly inhibited by L-NAME (30 mg kg-1), whereas vasodilation by sodium nitroprusside (300 nM) was not affected. Vasomotor nerve-induced vasodilatation, induced by stimulation of the tenuissimus nerve after neuromuscular blockade by pancuronium in animals pretreated with guanethidine, was significantly attenuated by L-NAME, an effect also reversed by L-arginine. The vasodilatation in response to active contractions of the muscle induced by motor nerve stimulation as well as the vasodilator response elicited by graded perfusion pressure reductions were unaffected by L-NAME or NG-monomethyl-L-arginine (L-NMMA, 10(-4) M) administered topically. Our results indicate that endogenous nitric oxide formed from L-arginine is a modulator of microvascular tone in vivo. Furthermore, the results suggest that endogenous nitric oxide is required for vasomotor nerve-induced vasodilatation, whereas it does not appear to play a role in myogenic vasodilatation or functional hyperaemia in this tissue.     

Effects of histamine H1-receptor blockade on respiratory and cardiac manifestation of systemic anaphylaxis

Summary In vivo anaphylaxis is associated with respiratory distress and cardiovascular failure. The present investigation was designed to further characterize respiratory and cardiac anaphylactic events. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin together with Freund's adjuvant. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed application of the antigen induced an initial increase of left ventricular pressure which was followed by a rapid decrease 5 min after antigenic challenge. Enddiastolic left ventricular pressure increased within 3 min, thus indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, heart rate steadily decreased. All animals died within 15 min. Simultaneously with cardiac anaphylactic malfunction, severe arterial hypoxia and carbon dioxide retention occurred, revealing respiratory distress.Histamine is known as a potent bronchoconstrictor via histamine H₁-receptor stimulation. Administration of H₁-recpetor antagonists to improve respiration may therefore provide further information on the contribution of pulmonary malfunction to anaphylactic cardiovascular shock. Therefore, additional experiments were performed with sensitized guinea pigs pretreated with the histamine H₁-receptor blocker mepyramine. In these experiments the antigenic challenge induced a dissociation of cardiac and respiratory manifestation of anphylaxis. Despite inhibition of hypoxia and carbon dioxide retention, left ventricular pump failure and occurrence of myocardial ischemia were delayed but not suppressed.It is concluded that histamine is an important mediator of anaphylactic respiratory distress. However, vasoactive anaphylactic mediators other than histamine are primarily involved in anaphylactic cardiac malfunction occurring during the later phase of systemic anaphylaxis.Supported by grant Fe 250/1-1 from the Deutsche Forschungsgemeinschaft (DFG).     

Die extravasale Komponente des Coronarwiderstandes mit steigendem linksventrikulären Druck

Summary In experiments on anaesthetized dogs the arterial blood pressure and the left ventricular pressure were enhanced by intraarterial blood transfusion. The circumflex branch of the left coronary artery was perfused by constant blood pressure at 65, 100 or 200 mm Hg. After elimination of the sinus node the heart rate was kept constant at 150 beats per minute by electrical stimulation of the right auricle. The metabolically regulated component of coronary resistance of the circumflex branch was kept constant by a maximal pharmacological dilatation. On this condition the coronary blood flow decreases with increasing left intraventricular systolic pressure. The coronary resistance increases. The increasing coronary resistance with increasing intraventricular blood pressure is caused by an enhancement of the extravascular component because the perfusion pressure and hematocrit were constant, and the coronary vessel maximal dilated. The rise of coronary resistance with increasing intraventricular blood pressure depends on the height of perfusion pressure. Low perfusion pressure is combined with a marked increase, while the increase is small in the experiments with high perfusion pressure. The pathophysiological significance of the results has been discussed.

     

激素对脑死亡猪心脏功能的保护及血清降钙素基因相关肽和内皮素1的影响**

背景：激素可以减轻脑死亡供体心脏的缺血再灌注损伤,减少炎症因子释放,起到保护脑死亡后供体心脏的作用。 目的：进一步验证激素对脑死亡猪心脏功能的保护作用及血清中降钙素基因相关肽和内皮素1的影响。 方法：版纳小耳猪14头,随机分为对照组和糖皮质激素组。用缓慢颅内加压法建立脑死亡模型,激素组予模型建立前半小时6 mg/kg甲泼尼龙琥珀酸钠静脉注入,对照组不用激素。分别予成模后0,1,3,6,9 h监测平均动脉压、左室射血分数,并测定血清中降钙素基因相关肽和内皮素1水平。 结果：激素组各时段平均动脉压、左室射血分数明显高于对照组(P < 0.05)。激素组血清中降钙素基因相关肽下降缓慢,内皮素1升高延缓,与对照组相比差异有显著性意义(P < 0.001)。提示激素可有效保护脑死亡期的心脏功能,其机制可能与减少炎症反应、增加心肌供能、维持内环镜稳定有关。.18.008     

Effects of histamine H1- and H2-receptor antagonists on cardiovascular function during systemic anaphylaxis in guinea pigs

The heart is a target organ of anaphylaxis. In isolated perfused hearts, an anaphylactic reaction is characterized by arrhythmias, coronary constriction, and severe impairment of ventricular contractile force. Various mediators such as PAF, thromboxane A₂ and leukotrienes, are responsible for anaphylactic coronary constriction and negative inotropic effects. The cardiac effects of anaphylactic histamine release are related to the stimulation of two antagonistic receptor types. Histamine induces atrioventricular conduction delay and constriction of the epicardial coronary vessels via H₁-receptor stimulation. H₂-receptors, however, mediatecoronary vasodilation and an increase in heart rate and myocardial contractility. It may therefore be concluded that administration of histamine H₂-receptor antagonists is disadvantageous. During anaphylactic states, the cardiodepressive effects of the other mediators of anaphylaxis are unmasked, resulting in a sustained coronary constriction and impairment of myocardial contractility. To verify this speculation, we investigated the effects of H₁- and H₂-receptor antagonists on cardiovascular function of guinea pigs during systemic anaphylaxis.In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed administration of the antigen induced severe cardiac dysfunction. Within a few minutes, cardiac output markedly decreased and left ventricular end-diastolic pressure increased significantly, indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, arrhythmias occurred in terms of an atrioventricular block. After 4 min, blood pressure rapidly declined. All animals died within 12 min. Pretreatment with the selective H₁-receptor antagonist astemizol (5 mg/kg i.v.) delayed the onset of myocardial ischemia, arrhythmias and cardiac pump failure. After 10 min, however, left ventricular contractility and blood pressure steadily declined, leading to severe hypotension within 30 min. In the case of a pretreatment with astemizol (5 mg/kg i.v.) and the H₂-receptor antagonist famotidine (10 mg/kg i.v.), no relevant changes of cardiovascular function were seen compared to pretreatment with astemizol alone. It is therefore concluded that endogenous histamine, via H₁-receptor stimulation plays an important part during the early phase of systemic anaphylaxis, whereas mediators other than histamine are involved at a later stage of the process. Furthermore, H₂-receptor-mediated effects are of minor importance in cardiovascular manifestation of anaphylaxis. Pretreatment with H₂-receptor antagonists has no detrimental effects on cardiovascular function during anaphylactic reactions in guinea pigs underin vivo conditions.Supported by grant Fe250/1-1 from the Deutsche Forschungsgemeinschaft (DFG).     

Role of nitric oxide in local blood flow control in the anaesthetized dog

Intravenous infusion of N ^G-nitro-L-arginine methyl ester (L-NAME), a potent inhibitor of nitric oxide (NO) formation from L-arginine, provokes marked rises in arterial blood pressure by increasing peripheral resistance. In order to further evaluate the contribution of basal NO-formation to control of organ blood flow, regional blood flow distribution within the myocardium, kidney and brain areas was assessed using the tracermicrosphere technique in anaesthetized dogs. After L-NAME (20 mg kg^–1 i.v.) kidney perfusion was homogeneously reduced by 55% in the entire cortex and the outer medulla. Within the left ventricular myocardium regional blood flow significantly decreased only in sub epicardial layers (–12%), whereas within the entire right ventricle regional blood flow was reduced by 19–24%. A close inverse relationship was found between all changes in regional myocardial blood flows observed after L-NAME and the respective control values. No significant changes in regional blood flow in different areas of the brain were detectable after L-NAME. It is concluded that the contribution of basal NO formation varies greatly between different organs and exhibits significant regional differences within the heart. It is possible that local metabolic mechanisms may compensate functionally for the inhibition of NO synthesis.