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T Podzuweit

Publications and source records attributed to T Podzuweit.

13 recordsLinked to original sources
PubMed1992

Potential arrhythmogenic role of cyclic adenosine monophosphate (AMP) and cytosolic calcium overload: implications for prophylactic effects of beta-blockers in myocardial infarction and proarrhythmic effects of phosphodiesterase inhibitors.

Activation of the adrenergic nervous system appears to play a crucial role in the genesis of fatal arrhythmias associated with the very early stages of acute myocardial infarction. The second messenger of beta-adrenergic catecholamine stimulation, cyclic adenosine monophosphate (AMP), has established arrhythmogenic qualities, acting by an increase in cytosolic calcium, which potentially has three adverse electrophysiologic effects. First, stimulation of the transient inward current by excess oscillations of cytosolic calcium can invoke delayed afterdepolarizations, so that triggered automaticity can develop in otherwise quiescent ventricular muscle. Second, cyclic AMP can evoke calcium-dependent slow responses in depolarized fibers, so that conditions for reentry are favored. Third, excess cytosolic calcium can cause intercellular uncoupling with conduction slowing. Focal changes in cyclic AMP and cytosolic calcium promote the development of ventricular fibrillation. Beta-adrenergic blockade can limit the formation of cyclic AMP in ischemic tissue. Furthermore, by reducing sinus tachycardia it can lessen cytosolic calcium overload. Hence, beta-adrenergic blockade helps to prevent ventricular fibrillation in the early stages of acute myocardial infarction and protects from sudden death in the postinfarction phase. In congestive heart failure, abnormalities of cytosolic calcium patterns exist with cytosolic calcium overload. It is proposed that the adverse effects of phosphodiesterase inhibitors on the mortality rate in patients with congestive heart failure can be explained by increased rates of formation of cyclic AMP and the development of calcium-dependent arrhythmias. Because calcium is the ultimate messenger of cyclic AMP-induced arrhythmias and because cytosolic calcium is increased in heart failure, it will be difficult to develop positive inotropic agents that are free of the risk of sudden death.

Adrenergic beta-Antagonists↗
PubMed1991

Factors determining ventricular fibrillation after induced cardiac arrest.

Ventricular fibrillation following release of the aortic cross clamp is not uncommon. In 38 patients undergoing aortic valve replacement we investigated if this disturbance of rhythm is due to perioperative myocardial ischemia or due to deterioration of myocardial function prior to surgery. In all cases hypothermic cardioplegic arrest (Bretschneider) was used. The mean duration of ischemia was 49.39 +/- 10.46 minutes. After release of the aortic cross clamp in 17 of 38 patients ventricular fibrillation occurred. To find out which factors are responsible for the occurrence of ventricular fibrillation we performed a statistical analysis. Thereby we found out that the occurrence of ventricular fibrillation did not correlate with ischemia, the maximal level of myocardium-bound creatine kinase, the NYHA stage, or the left ventricular end diastolic pressure. The left-ventricular concentration of noradrenaline determined just before release of the aortic cross clamp showed a significant negative correlation with the occurrence of ventricular fibrillation. From our results we conclude that ischemic injury was not the determining factor for the occurrence of ventricular fibrillation in our study. We suggest that the significant correlation with reduced myocardial noradrenaline content demonstrates that myocardial deterioration prior to surgery is the determining factor for the occurrence of ventricular fibrillation.

Analysis of Variance↗
PubMed1991

Absence of xanthine oxidoreductase activity in human myocardium.

STUDY OBJECTIVE: The aim was to examine whether or not xanthine oxidase activity may be a significant source of oxygen derived free radicals in the human heart. DESIGN: Xanthine oxidoreductase activity of human myocardium was assayed in vitro. In addition, tests were performed to assess whether or not endogenous inhibitors of the enzyme were present in myocardial homogenates. The enzyme assay was based on high performance liquid chromatography with electrochemical and/or radiochemical detection of hypoxanthine, xanthine, and urate. SUBJECTS: Measurements were done on (a) isolated perfused rat myocardia and (b) left ventricular needle biopsies and papillary muscles obtained during elective cardiac surgery (chiefly aortic and/or mitral valve replacement and aortocoronary bypass) (n = 105 patients). MEASUREMENTS AND MAIN RESULTS: Homogenisation of human papillary muscles in buffer caused significant accumulation of hypoxanthine but not xanthine or urate. In addition, during incubation of crude myocardial homogenates with exogenous xanthine or hypoxanthine in the presence of NAD+ and/or O2 no production of urate was detected. Likewise, following aerobic incubation of papillary muscle homogenates with 14C-hypoxanthine neither 14C-xanthine nor 14C-urate were formed. Absence of xanthine oxidising activity was also observed with human papillary muscle extracts that were subjected to either ultrafiltration or gel filtration. In contrast, the rat heart was found to contain abundant xanthine oxidoreductase activity. The rat heart enzyme was inhibited by both allopurinol and oxypurinol but remained active when mixed with human papillary muscle homogenates. CONCLUSIONS: These findings show absence of xanthine oxidase and xanthine dehydrogenase activities in human myocardium, indicating that xanthine oxidase is not a source of oxygen derived free radicals in the human heart.

Adolescent↗
PubMed1990

[Effect of the duration of reperfusion on metabolic recovery during unloading of the hypertrophic heart following induced heart arrest].

The methods of cardioplegia used today are not always able to sufficiently protect the hypertrophied heart. The present study investigated if a recovery period of 30 min before the end of ECC improves metabolic recovery of the heart in comparison to a recovery period of 15 min before terminating extracorporeal circulation. A clinical study was performed of patients undergoing aortic valve replacement. In one group reperfusion was performed for 15 min and in the second group for 30 min before the conclusion of extracorporeal circulation. The concentration of high energy phosphates in the left ventricle was determined at the end of the ischemic period, after 15 min and after 30 min of reperfusion. The behavior of the myocardial metabolites of the two groups showed no differences. Creatinephosphate increased continuously in both groups, while adenosine triphosphate and the adenonucleotide pool did not change during the reperfusion period. From our results we conclude that under the conditions given in our study a recovery period of 15 min is sufficient for metabolic recovery and prolongation of reperfusion before termination of extracorporeal circulation do not improve metabolic recovery.

Adenosine Triphosphate↗
PubMed1989

The anti-arrhythmic effects of myocardial ischaemia. Relation to reperfusion arrhythmias?

Ventricular tachycardia was induced in the intact non-ischaemic pig heart by intramyocardial or intracoronary infusions of noradrenaline or N6, O2'-dibutyryl-cAMP. The chemically induced tachycardia was consistently stopped within 10 to 30 s by occluding the coronary artery supplying the infusion area. This ischaemic effect was readily reversed by coronary reperfusion, with ventricular tachycardia resuming within seconds after release of the occlusion. In contrast to the immediate effect of myocardial ischaemia, it took several minutes for the tachycardia to cease after the infusion of arrhythmogenic compounds was stopped. Pacing experiments showed that the effect of myocardial ischaemia on ventricular tachycardia was probably not due to a conduction block. The anti-arrhythmic property of myocardial ischaemia was separate from its known effect of decreasing the ventricular fibrillation threshold for electrical stimulation. The increased vulnerability of the acutely ischaemic myocardium to fibrillation was apparent in experiments in which ectopic activity was induced in the non-ischaemic part of the myocardium. In these experiments ventricular fibrillation consistently ensued within 6 min following distal occlusion of the anterior descending coronary artery. By contrast, ventricular fibrillation was not precipitated by coronary artery occlusion or local infusion of arrhythmogenic compounds alone. Cyclic AMP was shown to accumulate in ischaemic myocardium. An association existed between cAMP accumulation and the intensity of early ischaemic arrhythmias as well as reperfusion arrhythmias. The highest incidence of ventricular fibrillation was found during reperfusion, at peak myocardial cAMP levels. These findings suggest: (1) Noradrenaline and dibutyryl-cAMP exert arrhythmogenic effects preferentially in the intact, non-ischaemic myocardium, the effects being attenuated in ischaemic myocardium by a paradoxical anti-arrhythmic effect of ischaemia. (2) In the acutely ischaemic heart, ventricular fibrillation may be precipitated by the emergence of ectopic activity outside the ischaemic area. (3) Arrhythmias and fibrillation occurring early after reperfusion may be caused by unmasking the effects of excitants (eg, noradrenaline or cAMP) arising during the antecedent period of ischaemia.

Animals↗
PubMed1988

Preservation of myocardial energy-rich phosphates by retrograde application of Bretschneider cardioplegia during aortocoronary bypass surgery.

The efficacy of myocardial protection obtained by antegrade application of a cardioplegic solution was compared with that obtained by retrograde application via the coronary sinus. Myocardial preservation was assessed using biochemical parameters, i.e. tissue content of lactate, creatine phosphate, nucleotides, nucleosides and hypoxanthine. Nineteen patients undergoing routine aortocoronary bypass surgery were randomly allocated to a study group. During cardiac arrest induced by antegrade Bretschneider cardioplegia, myocardial tissue content of creatine phosphate dropped to 52% of its pre-ischemic value and degradation of nucleotides occurred, characterized mainly by an accumulation of adenosine. Retrograde cardioplegia prevented this catabolism of energy-rich phosphates completely during ischemic cardiac arrest and is therefore considered to be superior to antegrade cardioplegia.

Adenosine↗
PubMed1985

Protection of the hypertrophied human heart by adjusting regional myocardial temperature to a safe level.

Uneven distribution of temperature and the persistence of electro-mechanical activity after aortic cross-clamping are 2 factors limiting the myocardial protection during cardioplegic arrest, especially in hypertrophied hearts which are known to be extremely vulnerable to ischemia. In the present study regional myocardial temperature (T) was continuously controlled, and the time until arrest occurred (delta t) was determined in 61 patients undergoing aortic valve replacement. In addition, the myocardial contents of high energy phosphates and lactate were assessed. Three different cardioplegic solutions were employed: In the first group we used Bretschneider solution (Br), in the second group St. Thomas' solution (St), and in the third group the so-called "Hamburg cardioplegia" (H). During cardiac arrest the regional myocardial temperature was adjusted to temperatures not exceeding 15 degrees C by intermittent infusions of cold cardioplegic solution. We found a positive correlation between left ventricular muscle mass (LVMM) and delta t. A negative correlation existed between LVMM and adenosine triphosphate (ATP) contents at the end of the ischemic period. The cooling characteristics and delta t were significantly longer and the cooling to 15 degrees C was less rapid when H was used. Adenosine-triphosphate contents were well preserved during ischemia in all 3 groups. We conclude that all 3 cardioplegic solutions tested protect the hypertrophied myocardium adequately if the regional myocardial temperature does not increase above 15 degrees C during cardiac arrest. Hearts with a higher LVMM showed a decreased myocardial ATP content at the end of the ischemic period. Therefore, the LVMM may limit myocardial protection.

Adenosine Triphosphate↗
PubMed1978

An automatic device for freeze-clamping of cardiac tissue within a fraction of the contraction cycle.

An automatic quick-freeze clamping device has been developed. Opposed pneumatic pistons filled with aluminium caps previously cooled in liquid nitrogen are used to compress a portion (100 to 200 mg) of the myocardium to a 0.15 to 0.20 mm thick wafer, colling the tissue from 37 degrees C to -15 degrees C within 10 ms. The clamp is triggered electronically from the R-wave of the ECG. This tissue fixation by freezing within 10 ms is sufficiently rapid to study oscillations of myocardial metabolite levels during the contraction cycle of isolated perfused hearts of small mammals such as the rat and guinea pig whose rate is 4 to 5 beats per second.

Animals↗
PubMed1978

The role of cyclic adenosine monophosphate in adrenergic effects on ventricular vulnerability to fibrillation in the isolated perfused rat heart.

The relation between myocardial tissue cyclic AMP (cAMP) and the vulnerability to ventricular fibrillation was assessed in the isolated perfused rat heart by measurement of ventricular fibrillation threshold (VFT) and vulnerable period duration (VP). Exogenous dibutyryl cyclic AMP (DBcAMP) reduced VFT and increased VP by a concentration-related action whereas exogenous cAMP did not. Theophylline (1.0 mmol/liter) increased the tissue content of cAMP by 58% (P < 0.001) and caused a leftward shift in the concentration-response curve to DBcAMP. An effect of cAMP on VFT and VP could be shown in the presence of phosphodiesterase inhibition by theophylline. beta-1-Adrenergic receptor blockade with atenolol did not alter the concentration-response curve for VFT when DBcAMP was administered. Epinephrine (100 nmol/liter to 1 mumol/liter) also increased vulnerability to VF; this effect was accompanied by a concentration-related increase in tissue cAMP, but inconsistent changes in tissue ATP, phosphocreatine and potassium. The concentration-response curve of VFT to epinephrine was shifted leftward by theophylline and rightward by atenolol. The increases in vulnerability to fibrillation in the isolated perfused rat heart, in response to DBcAMP, theophylline or epinephrine, could be related more closely to changes of tissue cAMP than to effects on tissue high energy phosphates or potassium. The effect of epinephrine and theophylline on vulnerability to ventricular fibrillation is mediated via alterations in the intracellular level of cAMP in the isolated perfused rat heart.

Adenosine Triphosphate↗
PubMed1976

Cyclic adenosine monophosphate, ventricular fibrillation, and antiarrhythmic drugs.

It is proposed that the development of ventricular fibrillation in the context of ischaemic heart-disease and myocardial infarction can be related to accumulation of cyclic adenosine 3',5' monophosphate (A.M.P.) in the ischaemic zone. The known electrophysiological and metabolic actions of cyclic A.M.P. are consonant with the hypothesis, which also provides a framework for the better understanding of the action of antiarrhythmic drugs.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Preservation of high energy phosphates in hypertrophied human myocardium.

Hypertrophied hearts are extremely vulnerable to ischemia. In 61 patients with aortic valve disease undergoing surgery we investigated the quality of myocardial protection obtained with three different methods of crystalloid cardioplegia. To exclude the influence of temperature differences the regional myocardial temperatures were continuously measured and adjusted to the same level in all patients. Before and after ischemia and after 10 minutes reperfusion myocardial biopsies were taken and the high energy phosphates and lactic acid determined. In one group St. Thomas cardioplegia was used, in another Bretschneider cardioplegia and in the third the Hamburg method. There were no significant differences between the three groups at the end of ischemia and after 10 minutes reperfusion. After 10 minutes reperfusion the metabolic alterations caused by ischemia were in part reversible. From our results we conclude that each of the cardioplegias used is able to protect a hypertrophied heart adequately against ischemia during cardiac arrest.

Adenosine Diphosphate↗