Original Method for Evaluating Endothelial Vasomotor Function of Isolated Vessel in Experiment.

We describe a method for experimental assessment of endothelial dysfunction in an isolated using extracorporeal machine perfusion and vasoactive substrates agents (norepinephrine and acetylcholine). Quantitative assessment of endothelial vasomotor dysfunction was proposed, based on registration of changes in volumetric perfusate flow rate through the isolated vessel. Functional activity of the isolated aorta endothelium and total content of stable NO degradation products in blood plasma were studied in outbred white male rats after subtotal liver resection. Impaired vasodilation ability of the aorta and increased content of NO degradation products in blood plasma observed after surgery indicate the development of vasomotor endothelial dysfunction associated with oxidative stress, cholemia, and endotoxemia.

Experimental model of heart contusion.

The proposed experimental model reproduces the mechanism of isolated contusion of the heart resultant from the chest stroke against the steering wheel prop in a car accident. The conditions of experiment rule out the additional pathogenetic factors occurring in clinical practice (extracardiac injuries, alcohol intoxication, blood loss, pain, etc.) and hence, it is possible to study the mechanisms of developing myocardial dysfunction proper and its contribution to the course and outcome of the posttraumatic period. Clinical, hemodynamic, and pathomorphological equivalents of this kind of blunt injury of the heart were obtained.

[Introduction of new technologies in teaching basic and clinical pathophysiology].

The article contains data on teaching basic and clinical pathophysiology in Omsk state medical academy. Teaching process includes tests of the first and second level of difficulty, solving situational profession-oriented problems, quizzes, demonstration of patients and pathophysiological analysis of clinical syndromes, case reporting and recording.

[Principle energy substrate changing as a technique of myocardium protection against ischemic damage in experimental mechanic cardiac contusion].

By changing the principal energy substrate, trimetasidine has reduced severity of ischemic myocardial damage as shown by greater integrity of membrane structures, improvement of contractile and rhythmic functions, central hemodynamics and lethality early after experimental myocardial contusion.

[Cardioprotective effect of exogenous creatine phosphate in acute hemorrhage]. / Kardioprotektornoe deistvie ékzogennogo kreatinfosfata pri ostroi krovopotere.

Experiments on noninbred albino male rats under the conditions of the whole body and the isolated isovolumically contracting heart have shown that a substantial contribution to postresuscitative cardiac damages is made by energy deficiency that triggers a group of mechanisms of damaging cardiomyocytic membranes. Exogenous creatine phosphate (CP) reduces postresuscitative mortality rates, improves bioenergy, contractile and rhythmical functions of the heart, decreases the rate of myocardial lipid peroxidation, by showing as a whole a cardioprotective action. The latter is realized by directly protecting the cardiomyocytic sarcolemma and the improvement of energy metabolism is secondary. Despite the likely mediation of this effect, improved energy metabolism is undoubtedly a key point of the protective action of exogenous CP if the heart is postresuscitatively damaged.

[Role of disorders of metabolism in rat myocardium and endotoxemia in the pathogenesis of post-resuscitation cardiodepression]. / Rol' narushenii metabolizma v miokarde krys i éndotoksemii v patogeneze postreanimatsionnoi kardiodepressii.

The model of 4-min clinical death due to acute blood loss was used to study cardiac contractility, myocardial metabolism and causes of endotoxemia in early postresuscitation period. The investigations were made on the whole body, isolated, isovolemically contracting heart and isolated papillary muscle. A marked reduction in functional myocardial reserves, maximal within the first 24 hours of postresuscitation, with dominant defects in relaxation was seen. Pathogenetic factors responsible for cardiodepression are the following: hypoxia, impairment of bioenergetics, hyperactivation of lipid peroxidation, acidosis, membrane destruction, endotoxemia.

[The verapamil correction of postresuscitation damages to the heart]. / Korrektsiia verapamilom postreanimatsionnykh povrezhdenii serdtsa.

Disorders of systemic hemodynamics and myocardial contractility during the early postresuscitation period were examined in 132 outbred male rats resuscitated after 4-min clinical death from acute blood loss. The efficacy of adding verapamil (calcium ion antagonist) in a dose of 0.1 mg/kg to a complex of reanimation measures was assessed. Verapamil added to resuscitation procedures was conducive to an earlier repair of heart work and to a reduction of the early postresuscitation arrhythmias; it ensured a hemodynamic relief of the heart and decreased cardiodepression. Cardioprotective effect of verapamil was due to its ability to protect cell membranes from irreversible ischemic and reperfusion damage by preventing the postresuscitation calcium overloading of cardiomyocytes.

[The membrane-protective effect of carnosine in the post-resuscitation period after acute lethal blood loss]. / Membranoprotektornoe deistvie karnozina v postreanimatsionnom periode posle ostroi smertel'noi krovopoteri.

Activation of serum enzymes in male rats was detected during the postresuscitation period after 4-6-min clinical death as a result of membrane destruction. Increase in the rate of lipid peroxidation and impairments of energy metabolism in the myocardium were responsible for destruction of cardiomyocyte biomembranes. Administration of carnosine (25 mg/kg body weight) simultaneously with compensation for blood loss obviated the membrane lipid bilayer destruction and contributed to the development of the optimal conditions for membrane-bound enzymes.

[The pathogenesis and correction of disorders of the heart rhythm in the early post-resuscitation period]. / K patogenezu i korrektsii narushenii ritma serdtsa v rannem postreanimatsionnom periode.

The frequency and nature of heart rhythm disturbances have been studied in experiments on random-bred male rats who survived 4- and 6-min clinical deaths of acute blood loss. Using correlation analysis it has been shown that the leading pathogenetic arrhythmogenic factors are: catecholamine excess, as well as excess of free fatty acids, lipid peroxidation products, lactate and Ca-ATPase inhibition. The efficacy of preventive (gutimin, inderal, oxipiridin-6, isoptin) and therapeutic (carnozin, creatinphosphate) use of the drugs affecting pathogenetic mechanisms of heart arrhythmias and thus stabilizing bioelectrical heart activity in the early postresuscitation period has been observed.

Pathogenesis and pharmacorrection of early postresuscitation cardiac arrhythmia.

Effect of acute lethal blood loss on character and frequency of cardiac arrhythmias in postresuscitation period has been studied. Experiments were carried out on mongrel male rats resuscitated after 4- and 6-min clinical death caused by acute blood loss. Electric cardiac instability was found in early postresuscitation period. Pacemaker migration, paroxysmal ventricular tachycardia, blockades and extrasystole that lead to ventricular fibrillation were observed in 20 percent of cases. Supported by correlative analysis it has been established that the main arrhythmogenic factors are abundance of catecholamines, free fatty acids, dienic conjugates, lactate and inhibition of Ca dependent ATPase. Antiarrhythmogenic effects of antihypoxant gutimin, the beta-adrenoreceptor blocker inderal, antioxidant oxypiridin-6 were noticed after their separate administration before clinical death. The same effect of carnosine and phosphocreatine administered during resuscitation also was noticed.

Functional metabolic heart impairment after acute lethal hemorrhage followed by resuscitation.

Effects of acute lethal blood loss on postresuscitation heart impairment has been studied. Experiments were performed in mongrel male rats anesthesized with sodium pentobarbital (25 mg/kg). Functional metabolic heart impairments have been evaluated in different terms after resuscitation by isolated perfused heart method (Fallen et al., J. Appl. Physiol, 22 (1967) 836-839). It has been established that maximal heart injury occurs in the first hours after resuscitation. It is supported by the following findings: depression of myocardium contractile function grew; enzyme excretion from cardiomyocytes in coronary flow increased: efficacy of glucose utilization by means of carried function decreased; pyruvate excretion in coronary flow elevated. Because of severe course of postresuscitation period functional metabolic heart disturbances are more pronounced and preserved for a long time.