舌下微循环变化在猪失血严重程度评估中的应用价值

目的探讨舌下微循环变化在猪失血严重程度评估中的应用价值。 方法健康雄性白猪20只,实验猪的总血容量被评估为70 ml/kg,根据失血比例的不同分为4组：对照组、25%失血组、35%失血组和45%失血组,每组5只。比较各组动物失血前体质量、心率、平均动脉压、心输出量、血乳酸及微血管流动指数（MFI）和灌注血管密度（PVD）变化,并分别于失血后30 min、1 h、2 h、3 h、4 h,评估动物的平均动脉压、心输出量、血乳酸、MFI及PVD的变化。 结果各组动物失血前体质量、心率、平均动脉压、心输出量、血乳酸、MFI及PVD比较,差异均无统计学意义（F = 0.156、0.260、0.467、0.417、0.434、1.778、0.149,P均> 0.05）。随着各组动物失血量的增加,平均动脉压及心输出量于失血后30 min[（117 ± 8）、（56 ± 10）、（45 ± 4）、（31 ± 5）mmHg,（4.80 ± 0.54）、（3.32 ± 0.32）、（2.35 ± 0.37）、（1.67 ± 0.15）L/min]及失血后1 h [（123 ± 4）、（89 ± 6）、（67 ± 8）、（52 ± 8）mmHg,（4.79 ± 0.63）、（3.99 ± 0.37）、（2.75 ± 0.35）、（2.05 ± 0.39）L/min]逐渐下降（P均< 0.05）,血乳酸于失血后1 h逐渐增加[（1.12 ± 0.33）、（2.10 ± 0.25）、（3.74 ± 1.38）、（5.88 ± 1.48）mmol/L,P均< 0.05],MFI[（2.92 ± 0.09）、（2.47 ± 0.28）、（1.30 ± 0.14）、（0.87 ± 0.27）,P均< 0.05]及PVD水平[（4.95 ± 0.12）、（4.20 ± 0.54）、（2.98 ± 0.10）、（2.64 ± 0.31）,P均< 0.05]于失血后30 min逐渐下降。Pearson相关性分析显示MFI及PVD与平均动脉压（r = 0.903、0.923,P均< 0.05）、心输出量（r = 0.919、0.919,P均< 0.05）呈显著正相关,与乳酸水平呈显著负相关（r = -0.706、-0.745,P均< 0.05）。 结论舌下微循环监测可实时反映机体失血程度,有助于判断失血严重程度。     

Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure

AM5 (adrenomedullin 5), a newly described member of the CGRP (calcitonin gene-related peptide) family, is reported to play a role in normal cardiovascular physiology. The effects of AM5 in HF (heart failure), however, have not been investigated. In the present study, we intravenously infused two incremental doses of AM5 (10 and 100 ng/min per kg of body weight each for 90 min) into eight sheep with pacing-induced HF. Compared with time-matched vehicle control infusions, AM5 produced progressive and dose-dependent increases in left ventricular dP/dt(max) [LD (low dose), +56 mmHg/s and HD (high dose), +152 mmHg/s] and cardiac output (+0.83 l/min and +1.81 l/min), together with decrements in calculated total peripheral resistance (-9.4 mmHg/min per litre and -14.7 mmHg/min per litre), mean arterial pressure (-2.8 mmHg and -8.4 mmHg) and LAP (left atrial pressure; -2.6 mmHg and -5.6 mmHg) (all P<0.001). HD AM5 significantly raised PRA (plasma renin activity) (3.5-fold increment, P<0.001), whereas plasma aldosterone levels were unchanged over the intra-infusion period and actually fell in the post-infusion period (70% decrement, P<0.01), resulting in a marked decrease in the aldosterone/PRA ratio (P<0.01). Despite falls in LAP, plasma atrial natriuretic peptide and B-type natriuretic peptide concentrations were maintained relative to controls. AM5 infusion also induced significant increases in urine volume (HD 2-fold increment, P<0.05) and urine sodium (2.7-fold increment, P<0.01), potassium (1.7-fold increment, P<0.05) and creatinine (1.4-fold increment, P<0.05) excretion and creatinine clearance (60% increment, P<0.05). In conclusion, AM5 has significant haemodynamic, endocrine and renal actions in experimental HF likely to be protective and compensatory in this setting. These results suggest that AM5 may have potential as a therapeutic agent in human HF.     

Effect of high doses of Fentanyl on myocardial infarction and cardiogenic shock in the dog

Experimental myocardial infarction was produced in dogs by occlusion of the left circumflex coronary artery. Within 2–3h after occlusion, a necrotic zone was evident and the maximum rate of change of pressure of the myocardium of the left ventricle (LV dP/dt max.) decreased from 1192 ± 98 to 621 ± 100 mmHg/s; the cardiac output decreased from 3.0 ± 0.4 to 0.8 ± 0.1 1/min, the left ventricular pressure decreased from 137 ± 10 to 82 ± 9 mmHg, and the mean aortic blood pressure decreased from 60 ± 2 to 49 ± 2 mmHg. The total peripheral resistance increased from 20.4 ± 2 to 69 ± 7 (arbitrary units), and the pulse rate increased from 158 ± 9 to 160 ± 12 beats/min. There was no significant change in pressure-time index and left ventricular end-diastolic pressure. Fentanyl, a central analgesic which is the most potent, shortest acting, fastest acting, and least toxic opiate, was administered in high doses (0.05 mg/kg). In dogs with experimental coronary occlusion, this drug caused a marked reduction in pulse rate from 160 ± 12 to 102 ± 6/min, a diminution of LV dP/dt max. from 621 ± 100 to 369 ± 98 and of cardiac output from 0.8 ± 0.1 to 0.6 ± 0.1 compared with post-occlusion values. There was no significant change in the other variables. However, the drug was effective in preventing ventricular fibrillation. The depressive effects of Fentanyl after occlusion of the left circumflex coronary artery could be reversed by atropine (0.1 mg/kg). Infusion of isoproterenol (0.01 ± 0.65 pg/min per kg in the dog after occlusion increased the LV dP/dt max. from 621 ± 100 to 1395 ± 82 mmHg/s and the cardiac output from 0.8 ± 0.1 to 2.4 ± 0.2 1/min, and the total peripheral resistance was reduced from 69 ± 7 to 31 ± 3 (arbitrary units). There was no significant change of left ventricular pressure and mean aortic blood pressure. This initial effect of this drug was pronounced but prolonged infusion for more than lh increased the incidence of fibrillation to 70%. It was concluded that Fentanyl did not prevent or reverse the marked decrease in cardiac output, LV dP/dt max. or left ventricular pressure associated with coronary occlusion. However, it appeared to be useful in controlling fibrillation in this condition, and if administered with atropine increased the long-term survival rate. Pre-treatment with Fentanyl before coronary occlusion elicited a protective effect on the heart by abolishing fibrillation and reducing the depressive responses associated with occlusion of the left circumflex artery.     

Combined angiotensin-converting enzyme inhibition and adrenomedullin in an ovine model of heart failure

Advances in the treatment of heart failure may require manipulation of neurohumoral responses to cardiac impairment in addition to the established strategy of angiotensin-converting enzyme (ACE) inhibition. Importantly, since new treatments are likely to be used in conjunction with ACE inhibition therapy, the effects of the combination of agents need to be assessed. Adrenomedullin (ADM) is a peptide with potent vasodilator and natriuretic actions. ADM and an ACE inhibitor (captopril) were administered for 3 h both separately and together in eight sheep with heart failure. Both ADM and captopril alone reduced arterial pressure, left atrial pressure (greater with captopril) and peripheral resistance, and increased cardiac output (greater with ADM). Compared with either treatment separately, combined ADM+captopril produced directionally similar but significantly greater changes in all haemodynamic variables (particularly falls in blood pressure). ADM increased renal sodium and creatinine excretion and creatinine clearance, and maintained urine output. Captopril and ADM+captopril reduced creatinine excretion and creatinine clearance, while urine volume and sodium excretion were not significantly altered. Plasma renin activity rose with all active treatments, whereas angiotensin II levels rose during ADM, but fell during captopril and ADM+captopril. Aldosterone was reduced by all active treatments. ADM+captopril reduced plasma noradrenaline (norepinephrine). In conclusion, short-term co-treatment with ADM and an ACE inhibitor produced significantly greater decreases in ventricular filling pressures and cardiac afterload, and increases in cardiac output, compared with either treatment alone. Despite the greater falls in blood pressure (and presumably renal perfusion pressure), renal function was maintained at a level similar to that observed with captopril alone.     

Urocortin 2 combined with angiotensin-converting enzyme inhibition in experimental heart failure

Ucn2 (urocortin 2) is a recently discovered peptide with therapeutic potential in heart failure. As any new treatment is likely to be used in conjunction with standard ACEI (angiotensin-converting enzyme inhibitor) therapy, it is important that the combined effects of these agents are assessed. In the present study, we investigated the effects of Ucn2 and an ACEI (captopril) administered for 3 h, both separately and together, in eight sheep with pacing-induced heart failure. Ucn2 and captopril alone both increased CO (cardiac output; Ucn2>captopril) and decreased arterial pressure (captopril>Ucn2), left atrial pressure (Ucn2>captopril) and peripheral resistance (Ucn2=captopril) relative to controls. Compared with either treatment alone, combined treatment further improved CO and reduced peripheral resistance and cardiac preload, without inducing further falls in blood pressure. In contrast with the marked increase in plasma renin activity observed with captopril alone, Ucn2 administration reduced renin activity, whereas the combined agents resulted in intermediate renin levels. All active treatments decreased circulating levels of aldosterone (Ucn2+captopril>Ucn2=captopril), endothelin-1 and the natriuretic peptides (Ucn2+captopril=Ucn2>captopril), whereas adrenaline (epinephrine) fell only with Ucn2 (Ucn2+captopril=Ucn2), and vasopressin increased during captopril alone. Ucn2, both separately and in conjunction with captopril, increased urine output, sodium and creatinine excretion and creatinine clearance. Conversely, captopril administered alone adversely affected these renal indices. In conclusion, co-treatment with Ucn2 and an ACEI in heart failure produced significantly greater improvements in haemodynamics, hormonal profile and renal function than achieved by captopril alone. These results indicate that dual treatment with these two agents is beneficial.     

A sternal accelerometer does not impair hemodynamics during piglet CPR

Aim

To determine whether the residual weight of a 260 g sternal accelerometer/force feedback device (AFFD) adversely affects hemodynamics during cardiopulmonary resuscitation in a piglet model of ventricular fibrillation cardiac arrest.

Methods

After induction of ventricular fibrillation, cardiopulmonary resuscitation was provided to ten piglets (10.8 ± 1.9 kg) for 12 min while maintaining aortic systolic pressure of 80-90 mmHg during four 3-min periods with or without an AFFD on the chest. Cardiac output and left ventricular myocardial blood flow were determined by neutron-microsphere technique.

Results

Using a linear mixed-effect model with residual maximum likelihood estimation to control for changes in cardiopulmonary resuscitation hemodynamics over time, cardiac output and myocardial blood flow did not differ with AFFD versus without AFFD. During the first 6 min, mean (±SEM) cardiac outputs were 0.42 (±0.05) L/min with AFFD versus 0.31 (±0.04) L/min without AFFD, and median left ventricular myocardial blood flows were 40.5 (±7.3) mL/min/100 g with AFFD versus 40.4 (±5.0) mL/min/100 g without AFFD. The mean right atrial diastolic pressures and coronary perfusion pressures were also not different (8 ± 0.7 mmHg versus 8 ± 0.9 mmHg and 16 ± 2 mmHg versus 16 ± 2 mmHg, respectively, during the first 6 min of CPR).

Conclusion

The use of a 260 g accelerometer/force feedback device designed for real-time feedback to the rescuer during resuscitation efforts did not adversely affect cardiac output or left ventricular myocardial blood flow during 12 min of chest compressions in a piglet model of ventricular fibrillation cardiac arrest.     

地尔硫䓬对离体大鼠心肌缺血再灌注损伤影响的研究

目的探讨地尔硫䓬对离体大鼠心肌缺血再灌注损伤的影响及其机制。 方法33只大鼠随机分为3组：正常对照组（N组）、缺血再灌注组（I-R组）、地尔硫䓬＋缺血再灌注组（D/I-R组）。N组持续灌流K-H液150 min;I-R组K-H液稳定灌流30 min后,结扎前降支30 min,继以K-H液再灌注90 min;D/I-R组给予地尔硫䓬（5 μmo/L）再灌注15 min,继以K-H液再灌流75 min。记录并分析各组大鼠左心室发展压、左心室内压力最大上升/下降速率（±dp/dtmax）、再灌注心律失常评分、心肌梗死面积以及各组左心室心尖组织的线粒体乙醛脱氢酶2（ALDH2）、Bcl-2以及Bax的mRNA基因与蛋白表达水平。 结果（1）左心室发展压D/I-R组再灌注30 min与45 min比I-R组压力明显升高［（92.68±5.09）mmHg vs（75.77±5.33）mmHg;（90.39±4.29）mmHg vs（72.34±7.49）mmHg;1 mmHg=0.133 kPa］,差异均具有统计学意义（F=72.81、51.92,P均=0.001）。（2）±dp/dtmax D/I-R组再灌注30 min与45 min时均比I-R组升高［＋dp/dtmax：（2885.45±286.47）mmHg vs （2063.64±105.57）mmHg;（2712.73±236.52）mmHg vs（2053.64±92.33）mmHg;-dp/dtmax：（2214.55±104.63）mmHg vs （1710.91±217.97）mmHg;（2119.09±84.43）mmHg vs（1544.55±207.72）mmHg］,差异均具有统计学意义（F=64.22、70.55、69.77、54.64,P均=0.001）。（3）N组仅有室性期前收缩的发生,未发生心室颤动、室性心动过速;D/I-R组出现室性期前收缩的个数较N组增加,差异具有统计学意义（P=0.001）;I-R组室性心动过速发生率高于D/I-R组,心室颤动时程与室性心动过速时程均较D/I-R组增加,差异具有统计学意义（P=0.013、0.049、0.001）;再灌注心律失常评分I-R组评分［5（3,6）,57.36］高于D/I-R组［3（1,4）,34.77］,差异具有统计学意义（P=0.001）。（4）心肌梗死面积I-R组高于D/I-R组［（55.51±1.43）% vs （17.01±1.13）%］,差异具有统计学意义（P<0.01）。（5）I-R组线粒体ALDH2表达明显减少。D/I-R组线粒体ALDH2表达与I-R组比较减少,但差异无统计学意义（P=0.11）,Bcl-2、Bax的表达均增加,D/I-R组Bcl-2/Bax的比值较I-R组增大（0.44 vs 0.22）,差异具有统计学意义（P=0.001）。 结论地尔硫䓬处理后能够减少缺血再灌注损伤。其保护作用机制之一可能是通过上调Bcl-2下调Bax的基因和蛋白表达,减少心肌细胞的凋亡,但其并不是通过上调线粒体ALDH2的基因与蛋白来实现。     

Circulating adrenaline and blood pressure: the metabolic effects and kinetics of infused adrenaline in man

Abstract. Six normotensive volunteers were infused with L-adrenaline at 001, 003, 005, 0075 and 010 μg/kg^-1 min^-1, each increment lasted 10 min. Plasma adrenaline rose from 0–27 to 4–61 nmol/1, and there were dose-related increases in plasma renin activity, blood glucose, plasma cyclic AMP and plasma free fatty acids, but not in plasma noradrenaline and cyclic GMP. Levels of circulating adrenaline previously noted in essential hypertensives had minimal cardiovascular effects. The secretion rate of adrenaline and its rate of clearance from the circulation were calculated from plasma samples taken during an hour-long infusion (0–083 ± 0006 μg kg^-1 min^-1) of L-adrenaline in the same individuals. The secretion rate ranged from 1 40 to 601 nmol/min with a mean (±SEM, 6) of 2–82 ±0–76 nmol/min. Mean clearance (±SEM, 6) was 9–41 ± 1 -37 1/min and ranged from 4–86 to 14.611/min. The decline of plasma adrenaline following the infusion was biexponential.
Plasma adrenaline is unlikely to be of primary importance in the elevation of blood pressure, either directly, via renin release or by noradrenaline release via presynaptic beta receptors. However, variation in clearance between subjects limits the use of plasma levels as an interindividual index of adrenal release of adrenaline. The relationship between sympathoadrenal activity and plasma adrenaline may be further perturbed by equilibration between the circulation and sites of tissue uptake. The lower levels of plasma adrenaline than of noradrenaline appear to result from both a slower rate of secretion and a higher rate of clearance from the circulation.     

Systolic Arterial Pressure Recovery After Ventricular Fibrillation/Flutter in Humans

Although the elective induction of cardiac arrest for implantable defibrillator insertion under general anesthesia is widely used, the hemodynamics of recovery of arterial blood pressure after cardiac arrest is not well-defined. Accordingly, the time course of recovery of systolic arterial pressure was studied in seven patients during the repetitive induction of ventricular fibrillation (n = 6) or ventricular flutter (n = 1). The mean number of episodes of cardiac arrest was 7 ± 2, and the mean drop in systolic pressure was 84 ± 16mmHg. The mean recovery time for systolic pressure was 10 ± 6 seconds, the average systolic pressure recovery rate was 13 ± 14 mmHg/sec, and the mean percent systolic pressure recovery was 94%± 9%. A negative logarithmic relation was found to exist between the rate of systolic arterial pressure recovery and the duration of ventricular fibrillation or flutter with a correlation coefficient of 0.68 to 0.97 (P < 0.05) in five of the seven patients. A linear relation between the time for systolic pressure recovery and duration of asystole was also defined. These results are consistent with the view that prolongation of ventricular fibrillation or flutter increases the duration of arterial pressure recovery through a negative effect on left ventricular contractility. Increased understanding of these relations may lead to increased safety of implantable defibrillator insertion.     

Vasopressin impairs brain, heart and kidney perfusion: an experimental study in pigs after transient myocardial ischemia

Introduction

Arginine vasopressin (AVP) is increasingly used to restore mean arterial pressure (MAP) in low-pressure shock states unresponsive to conventional inotropes. This is potentially deleterious since AVP is also known to reduce cardiac output by increasing vascular resistance. The effects of AVP on blood flow to vital organs and cardiac performance in a circulation altered by cardiac ischemia are still not sufficiently clarified. We hypothesised that restoring MAP by low dose, therapeutic level AVP would reduce vital organ blood flow in a setting of experimental acute left ventricular dysfunction.

Methods

Cardiac output (CO) and arterial blood flow to the brain, heart, kidney and liver were measured in nine pigs using transit-time flow probes. Left ventricular pressure-volume catheter and central arterial and venous catheters were used for haemodynamic recordings and blood sampling. Transient left ventricular ischemia was induced by intermittent left coronary occlusions resulting in a 17% reduction in cardiac output and a drop in MAP from 87 ± 3 to 67 ± 4 mmHg (p < 0.001). A low-dose therapeutic level of AVP (0.005 U/kg/min) was used to restore MAP to pre-ischemic values (93 ± 4 mmHg).

Results

AVP further impaired systemic perfusion (CO and brain, heart and kidney blood flow reduced by 29, 18, 23 and 34%, respectively) due to a 2.0-, 2.2-, 1.9- and 2.1-fold increase in systemic, brain, heart and kidney specific vascular resistances. The hypoperfusion induced by AVP was associated with an increased systemic oxygen extraction. Oxygen saturation in blood drawn from the great cardiac vein fell from 29 ± 1 to 21 ± 3% (p = 0.01). Finally, these effects were reversed 40 min after AVP was withdrawn.

Conclusion

Low dose AVP induced a pronounced reduction in vital organ blood flow in pigs after transient cardiac ischemia. This indicates a potentially deleterious effect of AVP in patients with heart failure or cardiogenic shock due to impaired coronary perfusion.     

硫化氢后处理对2型糖尿病大鼠心肌缺血再灌注损伤的保护作用及其与自噬潮的相关性研究

目的观察硫化氢后处理对2型糖尿病大鼠心肌缺血再灌注损伤（I/R）的保护作用及其与自噬潮的关系。 方法将60只成年雄性SD大鼠分为五组：假手术组：仅开胸并分离冠状动脉左前降支,但不结扎阻断血流;I/R组：于冠状动脉左前降支阻断30 min,再灌注4 h;氯喹（CQ）组：于术前1 h腹腔注射10 mg/kg,其余操作同I/R组;硫氢化钠（NaHS）组：于开放左冠状动脉再灌注即刻1 min内静脉注射硫氢化钠0.05 mg/kg,再灌注4 h;CQ + NaHS组：于术前1 h腹腔注射CQ,其余操作同NaHS组;每组12只。连续监测并记录大鼠平衡期15 min、缺血期15 min、再灌注1、2、4 h时大鼠心率、平均动脉压和心率-收缩压乘积（RPP）。再灌注4 h结束后分批处死大鼠并取心脏测定心肌梗死范围,并采用Western blotting法测定微管相关蛋白1轻链3（LC3）、Cathepsin B、Beclin-1、P62表达水平。 结果各组大鼠在各时间点心率的比较,差异无统计学意义（F=0.854,P=0.512）,而平均动脉压及RPP的比较差异均有统计学意义（F=5.182,P=0.007;F=5.082,P=0.008）。且再灌注期2、4 h时,NaHS组平均动脉压为（87 ± 8）mmHg、（91 ± 10）mmHg,RPP为（35.4 ± 4.6）次·mmHg·10³/min、（36.2 ± 5.8）次·mmHg·10³/min,NaHS组明显高于I/R组[平均动脉压分别为（72 ± 10）mmHg、（63 ± 6）mmHg,RPP分别为（28.7±5.8）次·mmHg·10³/min、（26.8 ± 3.8）次·mmHg·10³/min,P均< 0.05]。各组灌注期4 h时,心肌梗死范围区域所占比例及LC3、Cathepsin B、Beclin-1、P62比较差异均有统计学意义（F=96.907、71.164、43.594、57.180、35.967,P均< 0.05）,且NaHS组上述各指标均明显低于I/R组、CQ组、CQ + NaHS组（P均< 0.05）。 结论硫化氢可能通过修复自噬潮对2型糖尿病大鼠心肌I/R损伤发挥保护作用。     

Importance of the Site of Ventricular Tachycardia Origin on Left Ventricular Hemodynamics in Humans

Experimental animal data have indicated that the site of ventricular tachycardia origin and, hence, the degree of asynchronous contraction, may influence the hemodynamic tolerance during sustained ventricular tachycardia. However, data in man are scarce. We studied patients with preserved left ventricular function and absence of significant coronary artery disease. Ventricular tachycardia was simulated with rapid pacing (at 120 and 150 beats/min), performed randomly, from the right ventricular apex or the right ventricular outflow tract. Following pacing from one site, it was repeated from the alternate site. Compared to outflow tract pacing, QRS duration was significantly longer during rapid pacing from the apex. Left ventricular pressure was recorded using a micromanometer-tipped catheter. During sinus rhythm, peak systolic pressure was 142 ± 14 mmHg: at 120 beats/min, it decreased to 109 ± 12 mmHg during pacing from the apex and to 127 ± 21 mmHg during pacing from the outflow tract (P = 0.008). This difference diminished at 150 beats/min (101 ± 16 mmHg vs 112 ± 16 mmHg, respectively, P = 0.21). During sinus rhythm end-diastolic pressure was 13 ± 1 mmHg, which did not change significantly during pacing at 120 beats/min. During pacing at 150 beats/min, end-diastolic pressure increased to 21 ± 3 mmHg during pacing from the apex and to 16 ± 2 mmHg during pacing from the outflow tract (P = 0.005). Changes in first derivative of pressure and in isovolumic relaxation time constant were comparable during pacing from the two sites. Thus, it seems that tachycardias originating from the right ventricular outflow tract result in more favorable left ventricular hemodynamics, compared to those from the right ventricular apex     

Hypotensive and renal effects of Captopril

Abstract. The effects of Captopril on blood pressure and renal function were evaluated in ten patients with different degrees of hypertension. In seven, blood pressure was reduced after 7 weeks of therapy; in three it remained practically unchanged. No correlation was found between the standing plasma renin activity before treatment and the hypotensive response. Plasma renin activity increased significantly from the median value of 5.4 (range 1–16.7) to 9.5 (range 2.6–19.8)ngml¹ h¹ (P< 005) and urine aldosterone significantly fell from 13 (range 2–3–52–5) to 7.4 (range 1.6–14) μg 24 h^-1 (P<001) during therapy. Renal plasma flow decreased from 534 (range 300–616) to 471 (range 333–606) ml min^-1, but the difference was not significant, and glomerular filtration rate fell significantly form 122 (range 64–143) to 88 (range 71–116) ml min^-1 (P<0–05). No urinary excretion of alpha₂-macroglobulin was observed during Captopril. 24 h proteinuria, albumin and transferrin clearance, alanine-amino transferase, gammaglutamyl transfer-ase and alpha glucosidase excretion rate and malate-dehydrogenase clearance remained unaltered throughout the treatment. This indicates that neither glomerular permeability nor renal tubular function were affected by the drug.     

Normal fluctuations in pulmonary artery pressures and cardiac output in patients with severe left ventricular dysfunction.

BACKGROUND: One barrier to accurate interpretation of changes in hemodynamic pressures and cardiac output is lack of data about what constitutes a normal fluctuation. Few investigators have examined normal fluctuations in these parameters and none have done so in patients with left ventricular dysfunction. AIMS: To describe normal fluctuations in pulmonary artery pressures and cardiac output in patients with left ventricular dysfunction. METHODS: Hemodynamically stable advanced heart failure patients (N=39; 55+/-6 years old; 62% male) with left ventricular dysfunction (mean ejection fraction 22+/-5%) were studied. Cardiac output and pulmonary artery pressures were measured every 15 min for 2 h. RESULTS: Mean+/-standard deviation fluctuations were as follows: pulmonary artery systolic pressure=7+/-4 mmHg; pulmonary artery diastolic pressure=6+/-3 mmHg; pulmonary capillary wedge pressure=5+/-3 mmHg; cardiac output=0.7+/-0.3 l/min. The coefficient of variation for fluctuations in pulmonary artery systolic pressure was 6.7%, in pulmonary artery diastolic pressure was 9.3%, in pulmonary capillary wedge pressure was 9.2%, and in cardiac output was 7.2%. CONCLUSIONS: Values that vary <8% for pulmonary artery systolic pressure, <11% for pulmonary artery diastolic pressure, <12% for pulmonary capillary wedge pressure, and <9% for cardiac output from baseline represent normal fluctuations in these parameters in patients with left ventricular dysfunction.     

Pyruvate improves cardiac electromechanical and metabolic recovery from cardiopulmonary arrest and resuscitation

Severe depletion of myocardial energy and antioxidant resources during cardiac arrest culminates in electromechanical dysfunction following recovery of spontaneous circulation (ROSC). A metabolic fuel and natural antioxidant, pyruvate augments myocardial energy and antioxidant redox states in parallel with its enhancement of contractile performance of stunned and oxidant-challenged hearts. This study tested whether pyruvate improves post-arrest cardiac function and metabolism. Beagles were subjected to 5 min cardiac arrest and 5 min open-chest cardiac compression (OCCC: 80 compressions min(-1); aortic pressure 60-70 mmHg), then epicardial dc countershocks (5-10 J) were applied to restore sinus rhythm. Pyruvate was infused i.v. throughout OCCC and the first 25 min ROSC to a steady-state arterial concentration of 3.6+/-0.2 mM. Control experiments received NaCl infusions. Phosphocreatine phosphorylation potential (approximately PCr) and glutathione/glutathione disulfide ratio (GSH/GSSG), measured in snap-frozen left ventricle, indexed energy and antioxidant redox states, respectively. In control experiments, left ventricular pressure development, dP/dt and carotid flow initially recovered upon defibrillation, but then fell 40-50% by 3 h ROSC. ST segment displacement in lead II ECG persisted throughout ROSC. Approximately PCr collapsed and GSH/GSSG fell 61% during arrest. Both variables recovered partially during OCCC and completely during ROSC. Pyruvate temporarily increased approximately PCr and GSH/GSSG during OCCC and the first 25 min ROSC and enhanced pressure development, dP/dt and carotid flow at 15-25 min ROSC. Contractile function stabilized and ECG normalized at 2-3 h ROSC, despite post-infusion pyruvate clearance and waning of its metabolic benefits. In conclusion, intravenous pyruvate therapy increases energy reserves and antioxidant defenses of resuscitated myocardium. These temporary metabolic improvements support post-arrest recovery of cardiac electromechanical performance.     

A comparison of resuscitation with packed red blood cells and whole blood following hemorrhagic shock in canines

Resuscitation with crystalloid and packed red blood cells has for the most part replaced the use of plasma and whole blood in the initial treatment of hemorrhagic shock. The effects of such changes on cardiovascular function following hemorrhagic shock remain largely unexplored. We examined cardiovascular function in anesthetized canines subjected to severe hemorrhagic shock. Mongrel canines of either gender were anesthetized with isoflurane and instrumented for measurement of arterial pressure, cardiac output, coronary flow, and left ventricular pressure and volume for the determination of end systolic elastance (Ees). Following a 30-min stabilization period, blood was rapidly removed to induce fixed pressure (mean arterial pressure = 35 mmHg) hemorrhagic shock for 90 min or until an arterial lactate of 7.0 mM was achieved. Animals were then resuscitated with 2/3 of the shed volume as lactated Ringer's and an equal volume of either whole blood (WB, n = 8) or packed red blood cells (PRBC, n = 10) resuspended in lactated Ringer's (LR) solution to replace expressed plasma volume. PRBC resuscitated dogs showed lower values of mean arterial pressure, cardiac output, rates of ventricular contraction and relaxation and myocardial work. Increasing the maintenance infusion rate of LR (10 mL/kg/h) following PRBC infusion normalized mean arterial pressure, but not other indices of cardiovascular function. Thus, WB, but not PRBC resuscitation restores normal myocardial function during resuscitation from severe hemorrhagic shock.     

Effects of ketamine on left ventricular performance.

The cariac response to anesthetic doses of ketamine hydrochloride was studied in dogs, initially in the absence of other drugs and subsequently during beta adrenergic block with propranolol and combined beta adrenergic and cholinergic blockade with propranolol and atropine. Ketamine (4 mg/kg) was injected into the left atrium or the jugular vein. Administration of ketamine alone resulted in increases in heart rate (61 beats/min, P smaller than .001), cardiac output and left ventricular systolic pressure, but left ventricular end-diastolic pressure and dP/dt max (maximum rate of change of left ventricular isovolumic pressure development) were unchanged. After propranolol, the increase in heart rate produced by ketamine was attenuated, and a transient fall in dP/dt max occurred. After propranolol and atropine, heart rate was not changed by ketamine, but dP/dt max fell and left ventricular end-diastolic pressure rose. Systemic vascular resistance was not altered by ketamine. It is concluded that administration of ketamine increases sympathetic discharge and reduces vagal discharge to the heart. In the absence of sympathetic and vegal control over the heart, the drug depresses myocardial contractility.     

Hemodynamics of Idiopathic Paroxysmal Atrial Fibrillation

The hemodynamics of induced atrial fibrillation (AF) was investigated in 15 patients (ages 58 ± 11 years) with paroxysmal AF presenting without organic heart disease or hypertension. A hemodynamic study was performed both during sinus rhythm and after the induction of AF. The mean heart rate increased from 73 ± 11 to 128 ± 18 beats/min (P < 0.001) after AF. Systolic and mean aortic pressures did not significantly change, and diastolic aortic pressure increased (78 ± 11 vs 89 ± 12 mmHg, P < 0.01). Left ventricular enddiastolic pressure decreased during AF (9 ± 3 vs 6 ± 2.6 mmHg, P < 0.005), whereas mean pulmonary wedge pressure increased (8 ± 2 vs 12 ± 4 mmHg, P < 0.001). Systolic pulmonary arterial pressure did not show significant variations, and there was a slight but statistically significant increase in the diastolic and mean pulmonary arterial pressures (P < 0.01). The right ventricular end-diastolic pressure decreased during AF (5.6 ± 2 vs 3.8 ± 2 mmHg, P < 0.01 j, whereas mean right atrial pressure showed a trend toward an increase. Stroke volume markedly decreased (P < 0.001) while the cardiac index did not significantly change. Systemic vascular resistance, pulmonary arteriolar resistance, and the arteriovenous O₂ difference showed no significant variations after the induction of AF. These results suggest that in subjects without organic heart disease, paroxysmal AF is well tolerated hemodynamicaily, and the rise in the atrial pressures during AF is not related to an increase in the ventricular end-diastolic pressure.     

Cardiovascular hypertrophy in diabetic spontaneously hypertensive rats: optimizing blockade of the renin-angiotensin system

The aim of the present study was to compare the antihypertrophic effects of blockade of the renin-angiotensin system (RAS), vasopeptidase inhibition and calcium channel antagonism on cardiac and vascular hypertrophy in diabetic spontaneously hypertensive rats (SHR). SHR with streptozotocin-induced diabetes were treated with one of the following therapies for 32 weeks: the angiotensin-converting enzyme (ACE) inhibitor captopril (100 mg/kg); the angiotensin AT(1) receptor antagonist valsartan (30 mg/kg); a combination of captopril with valsartan; the vasopeptidase inhibitor mixanpril (100 mg/kg); or the calcium channel antagonist amlodipine (6 mg/kg). Systolic blood pressure and cardiac and mesenteric artery hypertrophy were assessed. Mean systolic blood pressure in diabetic SHR (200+/-5 mmHg) was reduced by captopril (162+/-5 mmHg), valsartan (173+/-5 mmHg), mixanpril (176+/-2 mmHg) and amlodipine (159+/-4 mmHg), and was further reduced by the combination of captopril with valsartan (131+/-5 mmHg). Captopril, valsartan and mixanpril reduced heart and left ventricle weights by approx. 10%. The combination of captopril and valsartan further reduced heart weight (-24%) and left ventricular weight (-29%). Amlodipine did not affect cardiac hypertrophy. Only mixanpril and the combination of captopril and valsartan significantly reduced mesenteric weight. The mesenteric wall/lumen ratio was reduced by all drugs, and to a greater extent by the combination of captopril and valsartan. We conclude that optimizing the blockade of vasoconstrictive pathways such as the RAS, particularly with the combination of ACE inhibition and AT(1) receptor antagonism, is associated with antitrophic effects in the context of diabetes and hypertension. In contrast, calcium channel blockade, despite similar effects on blood pressure, confers less antitrophic effects in the diabetic heart and blood vessels.     

Effects of proximal ventricular septal pacing on hemodynamics and ventricular activation

Recently the use of alternate site pacing to improve cardiac function in patients with bradyarrhythmias has increased. In the present study, hemodynamics of right ventricular septal pacing were studied in seven dogs. A bipolar screw-in lead and endocardial lead were placed in the proximal right ventricular septum and right ventricular apex, respectively. The right ventricle was paced from each site. A conductance catheter and Millar catheter were inserted into the left ventricle to determine the left ventricular pressure and the pressure-volume loop. Cardiac output was measured using the thermodilution method. In five of the seven dogs, ventricular activation was documented by isochronal epicardial activation mapping during each pacing mode. Mean arterial pressure and cardiac output during septal pacing were significantly higher than during apical pacing (110 +/- 17 mmHg vs 100 +/- 18 mmHg; 1.00 +/- 0.39 L/min vs 0.89 +/- 0.33 L/min). The positive dp/dt during septal pacing was significantly higher than during apical pacing (2137 +/- 535 mmHg/s vs 1911 +/- 404 mmHg/s). End-systolic elastance during septal pacing was significantly higher compared to apical pacing (13.1 +/- 0.3 mmHg/mL vs 8.9 +/- 4.0 mmHg/mL). The ventricular activation time during septal pacing was significantly shorter than during apical pacing. The epicardial maps generated during septal pacing were similar to those from atrial pacing. We conclude that hemodynamics and interventricular conduction are less disturbed by proximal right ventricular septal pacing than apical pacing in dogs with normal hearts.