Ischemic preconditioning of the heart is referred as a manifest increase in tolerance of the myocardium to otherwise damaging ischemic insult, achieved by one or few consequent initial short exposures to ischemia, each followed by reperfusion of the ischemic area. Several mechanisms such as opening of collateral vessels, the action of catecholamines, inositol phosphates, G-proteins and/or adenosine; inhibition of mitochondrial ATPase, the effects of different endogenous protective substances like heat stress or shock proteins, etc., are believed to cooperate in the mechanism of induction of preconditioning or in maintaining its effect. The present study is an attempt to extend the present knowledge about preconditioning from two aspects: i.) the peculiarities of energy equilibrium in preconditioned myocardium including adaptation of cardiac sarcolemmal ATPases to ischemia and/or hypoxia, and ii) participation of a new endogenous cardioprotective substance in the mechanism of preconditioning. The energy equilibrium in preconditioning is characterized by adaptation of cardiac energy demands to the capacity of energy production and delivery decreased by anaerobiosis and is manifested by constant ratios between ATP, ADP, AMP and the sum of ADN. Principles are proposed that may enable a prediction and mathematical modelling of the balanced energetic state in the preconditioned myocardium. These principles are based on thermodynamics and involve besides others a more economic handling of ATP by sarcolemmal ATPases. The latter enzymes adapt themselves to lowered availability of ATP by decreasing besides their Vmax also their values of Km (increase in the affinity) for ATP and some of them even adjust their activation energy (the anaerobiosis-induced elevation of Ea.t. is missing).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

PubMedDate not supplied

Protective effect of 7-oxo-prostacyclin on myocardial function and metabolism during postischemic reperfusion and calcium paradox.

The effect of 7-oxo PGI2 on function and metabolism of postischemic reperfused (30-min ischemia and 30-min reperfusion) rat hearts was studied with special regard to calcium overload as one of the main factors of the postischemic reperfusion damage to the heart. The drug (50 micrograms/kg i.p.) was applied 48 h prior to starting the experiments on isolated rat hearts (Langendorff preparation at 37 degrees C and constant perfusion pressure of 65 mm Hg). A late protective effect of 7-oxo PGI2 was manifested by an improved recovery of heart function during reperfusion and calcium overload, better preservation of myocardial ATP contents during ischemia and also after calcium overload, as well as by a normalization of the lactate content, otherwise extremely increased during ischemia. Electron microscopic data also supported the above results. The beneficial effect of pretreatment with PGI2 may be explained not only by its vasodilating action, but more by its membrane stabilizing effect with a consequently decreased sodium accumulation, potassium loss, as well as intracellular calcium overload.

Animals↗

PubMedDate not supplied

[Psychosomatic aspects of breast carcinoma].

Psychological differences were compared between 25 female patients with carcinoma of the breast (mamma) and 25 patients with mastopathia cystica fibrosa. Our methods consisted in psychoanalytical interviews and MMPI-tests. We investigated the early childhood-period, the object relationships, the structurs of the personality and the psychological stress before the beginning of the physical illness. Patients with carcinoma of the breast show more frequent broken home situations, and inclination to idealize the past, depressive traits and a tendency to repress inner conflicts. The sexual behavior shows statistically more frequent abortions in the cancer group. In the beginning of the cancer we found statistically more frequent the loss of a meaningful personal relationships (e.g. death of the mother). Several differences between the personal structure were also found in the MMPI-tests.

Adult↗

PubMedDate not supplied

Uneven distribution of injuries in calcium paradox, postischemic reperfusion and by reactive oxygen species damaged heart. Histochemical and ultrastructural studies.

Under physiological conditions different parts of the heart reveal superspecialization of the myocardium reflected by biochemical, functional, structural and histochemical differences, which are even more pronounced under pathological conditions. Postischemic reperfusion, Ca paradox and injury caused by reactive oxygen species were found to result in transmurally unhomogenous damage of the ventricular wall. In the present experiments isolated perfused rat hearts were subjected to damage by the above mechanism and a different vulnerability of defined parts of the heart was observed. Activities of glycogen phosphorylase, SDH, beta-HBDH, and LDH were studied histochemically in both ventricles, the atria and the specialized conductive system of the heart. Marked decreases of activities were observed in the ventricular muscle. The enzyme activities were less decreased in the atrial muscle. Conductive fibres were the least affected tissue in this respect. The differential changes were most sensitively reflected by glycogen phosphorylase. The differences in transmural distribution of damage were shown to be dependent on a complex of specific factors such as intramural pressure gradient, transmural pressure, end-diastolic intraventricular pressure, differences in transmural vessel distribution, transmural hematocrit differences, blood flow, perfusate volume, and endothelial injuries of different origin. It can be concluded that differences in ultrastructure as well as in enzyme activities in different parts of the heart reflect functional, structural and metabolic heterogeneity of the different functional parts of the heart muscle.

Animals↗

PubMedDate not supplied

Protective effect of calmodulin inhibitors on reperfusion injury.

Activation of an intracellular calcium-calmodulin complex may play an important role in myocardial injury induced by ischemia and reperfusion. Chlorpromazine and trifluoperazine, calmodulin inhibitors, were used to enhance myocardial preservation by preventing harmful effect of intracellular calcium accumulation. The experimental model used one-hour LAD coronary occlusion and subsequent two-hour reperfusion in 70 dogs divided into four groups. Reperfusion alone significantly increased regional myocardial blood flow and left ventricular enddiastolic pressure and significantly reduced infarct size, dp/dt max, V max, mean aortic pressure, cardiac index and index of left ventricular minute work. Phenothiazines, applied at the 30th minute of occlusion significantly reduced infarct size, left ventricular enddiastolic pressure and index of systemic resistance and significantly increased dp/dt max, V max, cardiac index and regional myocardial blood flow in ischemic and border zones. The physiological results tightly correlated with the biochemical results and ultrastructural findings. The present study suggests that phenothiazines can improve cardiac performance and preservation of myocytes by preventing calcium stimulatory effect on degradative enzymes and may represent a potential clinical tool in modifying myocardial injury induced by ischemia and reperfusion.

Animals↗

PubMedDate not supplied

On the absorption of drugs using chronic dog ileal loop method.

The absorption rate of three model drugs, i.e., pentacaine (highly lipophilic), stobadine (moderately lipophilic) and acetylsalicylic acid (hydrophilic), was studied using the chronic dog ileal loop method. The drugs were dissolved either in 0.9% unbuffered solution of NaCl or in antacid mixture. When using 0.9% NaCl, the half-lives of absorption (t1/2 (dis)) of pentacaine and stobadine were (mean +/- SD) 23.2 +/- 7.8 min and 20.8 +/- 7.2 min, respectively. For stobadine a good agreement was found between its t1/2 (dis) from the ileum and its absorption half-life determined from blood concentrations after oral administration to dogs. The absorption of acetylsalicylic acid accounted for only 10-20% of the dose introduced into the loop over 45 min; thus, a reliable value of t1/2 (dis) could not be determined. The administration of unbuffered solution of NaCl into the loop was accompanied by rapid increase of pH from acidic to basic value. The antacid mixture failed to affect the absorption rate of the drugs studied. Sampling from the ileum was limited to 35-55 min due to rapid absorption of water. These results suggest that: 1) measurement of the absorption rate of some drugs, e.g., stobadine, by using the chronic dog ileal loop method may adequately predict their absorption rate after peroral administration to the dog, 2) interactions of antacids with drug absorption in the ileum may not play a significant role because of the strong buffering capacity of the ileum, and 3) rapid absorption of water from the ileum does not allow to reliably determine the value of t1/2 (dis) for slowly absorbed drugs.

Administration, Oral↗

PubMedDate not supplied

Further assessment of the protective effect of calmodulin inhibitors against reperfusion injury after acute coronary occlusion in the dog.

OBJECTIVE: To re-evaluate the suitability of chlorpromazine and trifluoperazine to prevent postischemic reperfusion injury of the myocardium. DESIGN: Acute occlusion (60 mins) and subsequent reperfusion (120 mins) of the left anterior descendent coronary artery with monitoring of hemodynamic, morphological and biochemical variables of the heart. SETTING: Experimental study. ANIMALS: Seventy adult mongrel dogs. INTERVENTIONS: Chlorpromazine (15 mg/kg body weight) or trifluoperazine (2 mg/kg body weight) given intravenously 30 mins after the onset of occlusion. MAIN RESULTS: Reperfusion alone increased the regional bloodflow and left ventricular end-diastolic pressure (P < 0.05 to 0.01), and reduced the size of the occluded area. Reperfusion also decreased the dp/dtmax, Vmax, mean aortic pressure, cardiac index, etc, but failed to improve cardiac ultrastructure and metabolism. Chlorpromazine or trifluoperazine induced a further reduction (P < 0.05 to 0.01) in infarct size, left ventricular end-diastolic pressure and systemic resistance index, and caused an increase in dp/dtmax, Vmax, cardiac index and regional bloodflow in the ischemic and border zones of the left ventricle. Moreover, these drugs preserved, to a certain extent, the metabolism of the myocardium and its ultrastructure. CONCLUSIONS: In spite of their considerable preventive effect, neither chlorpromazine nor trifluoperazine provided a complete prevention of reperfusion injury to the myocardium.

Animals↗