It has been implied that the increase of myocardial extracellular potassium activity [( K+]e) in the early stage of acute myocardial ischemia is a major cause of the increased likelihood of arrhythmia after acute coronary artery occlusion. There is also experimental evidence that some calcium antagonists reduce the occurrence of ischemia-induced early ventricular arrhythmias. In order to clarify the antiarrhythmic effect of gallopamil during the early phase of acute LAD occlusion, the influence of this calcium antagonist on the time course of [K+]e during acute ischemia was measured in open-chest anesthetized dogs using a K+-selective surface multielectrode. The regional myocardial blood flow was determined with 9 micron radioactive tracer microspheres. After application of gallopamil (bolus 25 micrograms/kg and infusion 2.5 micrograms/kg.min for 30 min) the maximal and mean rate of rise of [K+]e as well as the plateau of [K+]e reached during ischemia were significantly diminished compared with the control occlusions. 90 min after gallopamil, the rate of rise of [K+]e as well as the plateau of [K+]e reached were still significantly reduced, but 180 min after the gallopamil application, no significant differences between the time course of [K+]e and that of the two control occlusions could be found. Gallopamil significantly elevated myocardial blood flow in the non-ischemic area, but did not influence blood flow in the ischemic region. While collateral perfusion remains unchanged, the slowed and reduced increase of myocardial [K+]e during acute coronary artery occlusion may be an important component of the antiarrhythmic effect of gallopamil during early ischemia.

Animals↗

PubMedDate not supplied

Early changes in collateral blood flow to ischemic myocardium and their influence on bimodal vulnerability during the first 30 min of acute coronary artery occlusion in dogs.

Coronary collateral blood flow and its changes during the first 30 min of acute coronary artery occlusion were studied in 34 anesthetized dogs to clarify its influence on the vulnerability of the heart in this first arrhythmic phase. Collateral flow was determined with 9-micron tracer microspheres (TM) injected at 1, 10 and 30 min after acute proximal occlusion of the left circumflex (LCX, n = 30) or left anterior descending (LAD, n = 4) coronary artery. The post-mortem selective retrograde coronary angiography was used to evaluate the functional extent of preexisting coronary collaterals. After acute LCX occlusions collateral flow increased significantly (p less than 0.05) from 17.8 +/- 2.7 ml.(min.100 g)-1 (mean +/- SE; n = 13) at 1 min to 29.3 +/- 5.1 ml . (min . 100 g)-1 at 30 min of occlusion in animals with well-formed preexisting coronary collaterals (group 1), whereas it was very low (4.7 +/- 0.6 ml . (min . 100 g)-1; n = 13) and changed only slightly in dogs with poor collaterals (group 2). Most of these animals died by ventricular fibrillation (VF) before a second measurement could be carried out. In four dogs with poor collaterals but an unusually small LCX area (group 3), flow remained almost constant (11.0 +/- 4.7 versus 11.0 +/- 4.4 ml . (min . 100 g)-1) during this period. Similar results were obtained in animals with acute LAD occlusion (group 4). Ventricular extrasystoles (VES) mainly developed in animals with poor collaterals and respective low and almost unchanging collateral flow (group 2,3,4) while none or only a few VES occurred in dogs in which flow initially was clearly higher and increased significantly (group 1). The animals of group 1, 3 and 4 all survived the first arrhythmic phase, whereas all the animals of group 2 died by VF, either in the arrhythmic subphase Ia (n = 7) or Ib (n = 6). The results of the present study show that only the initial magnitude of flow is decisive for the development of VES and VF during the first arrhythmic phase, whereas the subsequent increase in flow is of no importance to the bimodal vulnerability in the first arrhythmic phase (subphases Ia and Ib). The in vivo measured critical minimal collateral flow of about 5 ml . (min . 100 g)-1 corresponds well with the survival limit (border between collateral state III and IV) previously determined by post-mortem retrograde coronary angiography.

Acute Disease↗

PubMedDate not supplied

Early shunting of 9 microns and 15 microns tracer microspheres from the acutely ischemic canine myocardium.

Recent reports have shown considerably differing results for myocardial shunting of 9 microns and 15 microns tracer microspheres (TMs) under various conditions. This could restrict the use of TMs for myocardial, especially collateral blood flow measurements. To determine the importance of coronary collateral blood flow and its early changes during the first 30 minutes after acute coronary artery occlusion (i.e. the 1st arrhythmic phase), we studied the shunting of 9 microns and 15 microns TMs from the ischemic myocardium during acute LAD ligation. In anesthetized dogs these TMs and subsequently Ringer solution were infused into the occluded coronary artery just distal to the ligation with constant low perfusion pressure. TM shunting (%S) into the lungs was then determined (%S = total lung radioactivity . 100/radioactivity infused). During a single LAD occlusion lasting 35 minutes (series I, n = 10) 9 microns TMs were infused immediately and 30 minutes after ligation, 15 microns TMs being infused after 15-20 minutes. In series II (n = 6) 9 microns TMs were infused immediately during the 1st, short (5 minutes) LAD occlusion. Following 90 minutes of reperfusion a 2nd LAD ligation (35 minutes) was performed with 9 microns TMs being infused immediately and 30 minutes after occlusion. During the first 30 minutes of acute coronary artery occlusion, TM shunting from the ischemic myocardium is negligible for 15 microns TMs (%S less than 0.5%; n = 5), whereas the mean 9 microns TM shunt of the early applied TM (i.e. A1, series I; n = 9; B2, series II; n = 6) amounts to a maximum of 1.21 +/- 0.2% (X +/- SEM). After 30 minutes of occlusion the mean 9 microns TM shunt amounts only to 0.71 +/- 0.15% (i.e. C1, series I; n = 4; C2, series II; n = 4). - In a coronary artery occlusion repeated once, 9 microns TM shunting, while increasing slightly due to the 90 minutes of reperfusion, still amounts to only 1.73 +/- 0.41% (n = 6). In three experiments 9 microns TMs were infused into the unoccluded, normally perfused LCX coronary artery during LAD occlusion. The mean LCX shunt value of 4% after a mean time of 25 minutes following TM infusion is in very good agreement with the 9 microns TM shunt values in the literature. These results clearly demonstrate that the TM technique with 9 microns microspheres is suitable for measuring changes in coronary collateral blood flow at least for a short time period after acute coronary artery occlusion.

Acute Disease↗

PubMedDate not supplied

The effects of lidocaine on the ventricular fibrillation threshold and primary ventricular fibrillation following acute experimental coronary occlusion.

Experiments were performed on 39 anaesthetized open-chest dogs (BW 16-33 kg) to examine the effect of lidocaine on the frequency of primary ventricular fibrillation (VF) and the time course of the ventricular fibrillation threshold (VFT) (train of stimuli-method) following acute coronary artery occlusion, and also to study the effects of lidocaine on the VFT of non-ischaemic heart at different therapeutic and high non-therapeutic doses. At effective plasma levels of lidocaine usually reached in clinical therapy (130-480 micrograms/l) there was no measurable increase in VFT compared to control values. The drop in VFT following acute ligation of the left anterior descending coronary artery (LAD) was neither eliminated nor even merely diminished. After occlusion of the left circumflex coronary artery (CIR), the incidence of spontaneous VF was not reduced in comparison to a control group. With regard to the doses administered and the plasma levels of lidocaine achieved, only the application of clinically extremely high or toxic doses resulted in increases in VFT in the non-ischaemic heart.

Acute Disease↗

PubMedDate not supplied

Nonhomogeneous electrophysiological changes and the bimodal distribution of early ventricular arrhythmias during acute coronary artery occlusion.

There is experimental evidence that the bimodally distributed ventricular arrhythmias (phases Ia and Ib) during the first 30 min after coronary occlusion (CO) in dogs are not due to the same mechanism. In 39 dogs we related the incidence of phases Ia and Ib to the time courses of excitation thresholds (ET), refractoriness (REFR), conduction times (CT) and effective refractory periods (ERP) at 6-12 epicardial electrode sites within the ischemic zone. The regional collateral myocardial blood flow (RMBF-tracer microsphere technique) was determined in 14 out of the dogs. This measurement only served for rough grouping into dogs with low and higher RMBF at the electrode sites during ischemia. REFR was determined as temporal recovery of excitability at a constant current strength of 4-6 times preocclusion ET. ERP was intermittently measured at 2.0-8.0 mA. At low RMBF ET, REFR and CT increased very inhomogeneously (dispersion of ET increased from 0.06 to 2.42 mA) 2-8 min after CO, leading to Ia-arrhythmias (also depending on infarct size) which terminated as ET, REFR and CT partially recovered 10-30 min after CO, their dispersions being still markedly elevated. With further recovery of these electrophysiological parameters the phases Ib subsided. On the other hand, the ERP diminished for the most part within the first 10 min after CO with only minor further decrease. Remarkably the dispersion of ERP did not significantly increase within the ischemic zone (from mean = 15 +/- 5 ms to 22 +/- 8 ms at low RMBF and from 14 +/- 6 ms to 18 +/- 9 ms at higher RMBF, p = ns). As a consequence of the homogeneous and constant shortening of the ERP, the time course of REFR mainly was determined by the nonhomogeneous alterations of ET. At a higher RMBF there were only minor electrophysiological alterations, and Ia- or Ib-arrhythmias did not emerge. These results indicate a strong relation of the Ia- and Ib-arrhythmias to the ischemia-induced time courses and dispersions of ET, REFR and CT but not of ERP within the ischemic area. Although the phases Ia relate to a strong increase of ET, REFR and CT and the Ib-arrhythmias to a partial recovery of these parameters, both the Ia- and Ib-arrhythmias seem to depend on a "critical" extent of electrophysiological inhomogeneity within a "critical" mass of ischemic but excitable myocardium.

Animals↗

PubMedDate not supplied

Changes in ventricular fibrillation threshold during repeated short-term coronary occlusion and release.

The time course of changes in VFT was determined during the 1st phase of arrhythmia following coronary occlusion and during consecutive reperfusion in five repeated periods of occlusion and reperfusion in 10 mongrel dogs (17--24 kg). VFT was determined using a square wave pulse series of 140 ms duration which was triggered by the R-wave of the ECG and placed into the vulnerable period of the cardiac cycle. After acute occlusion VFT decreased to a minimum level within a few minutes and then increased again slowly up to the control value which was reached about 20 min after the ligation. When the occlusions were repeated several times the extent of the decrease in VFT became increasingly less and its duration increasingly shorter until finally there was no significant decrease in VFT. Reperfusion after coronary occlusion led to an abrupt decrease in VFT within 1 min, followed by a rapid increase to the control value. This time course did not depend upon the number of prior occlusions. The results show that in the case of repeating short-term coronary occlusions one cannot expect comparable VFT time courses for the consecutive periods of occlusion except for the 1st and 2nd ones. Differing mechanisms leading to the occurrence of VF after coronary ligation and during reperfusion are discussed.

Animals↗

PubMedDate not supplied

Maximum contractility of the experimentally hypertrophied heart in situ and survival of the acute coronary occlusion.

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Acute Disease↗

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[Therapy of lidocaine-resistant arrhythmias following experimentally severe heart infarct by supplementary sympathicolysis, especially with atenolol].

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Animals↗