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Biomedical subjects

D J Hearse

Publications and source records attributed to D J Hearse.

At least 163 records · Page 9Linked to original sources
PubMed1989

Inability of chronic chemical sympathectomy to induce coronary collateral growth or development: studies in the rat heart in vivo.

The influence of chronic chemical sympathectomy on the extent of coronary collateral flow delivered to a zone of regional ischaemia following an acute coronary artery occlusion was examined in the rat. Male rats were randomly assigned to either 6-hydroxydopamine treated or vehicle treated groups (n = 20 in each group). Drug treated animals were injected with 6-hydroxydopamine intravenously as follows: day 1, 10 mg.kg-1; day 2, 50 mg.kg-1; days 7, 8, 14, 15, 21, 28, 35 and 42, 100 mg.kg-1. Control animals were injected in a similar manner with vehicle solution. On day 43, animals were anaesthetised, and their hearts were excised and perfused in the Langendorff mode at a perfusion pressure of 10 kPa. After 5 min the left main coronary artery was ligated and after a further 5 min, 153Gd labelled microspheres (10 microCi, 15 microns diameter) were infused via a side arm on the aortic cannula. This was followed within 3 min by the infusion of 3H-desmethylimipramine (5 microCi) via the same route. Disulphine blue dye was injected via the side arm within 1 min of the desmethylimipramine injection so as to delineate the perfused from the ischaemic region. The hearts were frozen in liquid nitrogen and freeze dried. The dried hearts were separated into ischaemic and non-ischaemic tissue on the basis of the blue dye coloration. The weighed samples were assessed for gamma and beta activity and the ratio of radioactive counts.g-1 in the ischaemic tissue to that of the non-ischaemic tissue was taken as an index of relative coronary collateral flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Coronary vascular responsiveness to 5-hydroxytryptamine before and after infusion of hyperkalemic crystalloid cardioplegic solution in the rat heart. Possible evidence of endothelial damage.

Using the isolated, Langendorff-perfused rat heart (n = 8 per group), we have studied the effects of 5-hydroxytryptamine and papaverine on coronary flow before and after a 30-minute infusion of hypothermic (20 degrees C), nonoxygenated cardioplegic solution containing potassium in a concentration of either 25 or 40 mmol/L. Before infusion of the 25 mmol/L potassium cardioplegic solution, both 5-hydroxytryptamine (1 x 10(-7) mol/L) and papaverine (5 x 10(-6) mol/L) caused similar increases in flow (+21.2% +/- 1.6% and +22.8% +/- 1.6%, respectively). After cardioplegia, the vasodilatory response to 5-hydroxytryptamine was completely lost and a slight vasoconstriction was observed (-0.2% +/- 1.2%). However, there was no significant change in the response to papaverine, which maintained a +23.7% +/- 1.4% vasodilation. With the cardioplegic solution containing a 40 mmol/L concentration of potassium, the initial responses to 5-hydroxytryptamine and papaverine were again similar (+21.5% +/- 2.5% and +24.1% +/- 3.0%, respectively). After cardioplegia, 5-hydroxytryptamine caused a significant vasoconstriction (-4.3% +/- 1.1%), whereas the response to papaverine was again maintained (+19.1% +/- 2.3%). The results of this study support the concept that hyperkalemic crystalloid cardioplegic solutions cause vascular damage possibly involving the endothelium or its function, which may adversely affect vascular responsiveness.

Animals↗
PubMed1989

Protection of the myocardium during global ischemia. Is crystalloid cardioplegia effective in the immature myocardium?

In pediatric cardiac operations, a high proportion of hospital deaths are believed to result from inadequate myocardial protection during the period of global ischemia. To investigate whether this may be due to an inherently lower resistance to myocardial ischemia or to the failure of conventional cardioplegia to afford adequate protection in the immature heart, we have conducted a series of studies with isolated hearts from neonatal (3 to 5 days old, body weight 6.3 to 13.4 gm) and adult (84 to 112 days old, 260 to 340 gm) rats. The efficacy of cardioplegia was assessed in neonatal hearts (n = 6 per group) subjected to various durations of normothermic ischemia, with and without a 2-minute preischemic infusion of the St. Thomas' Hospital cardioplegic solution. At all times studied, the use of cardioplegia resulted in a greater postischemic recovery of left ventricular developed pressure and first derivative of left ventricular pressure. After periods of ischemia lasting 30, 60, 90, 120, and 150 minutes in the absence of cardioplegia, left ventricular developed pressure recovered to 80% +/- 10%, 66% +/- 11%, 53% +/- 7%, 33% +/- 6%, and 21% +/- 4% of preischemic values, respectively; in the presence of cardioplegia, the values were 89% +/- 6%, 83% +/- 8%, 74% +/- 6% (p less than 0.05), 58% +/- 5% (p less than 0.05), and 41% +/- 7% (p less than 0.05), respectively. The corresponding values for first derivative of left ventricular pressure were 78% +/- 9%, 67% +/- 12%, 54% +/- 7%, 30% +/- 5%, and 19% +/- 3% in the absence of cardioplegia and 92% +/- 7%, 88% +/- 8%, 75% +/- 8%, 56% +/- 5% (p less than 0.05) and 39% +/- 6% (p less than 0.05) in the presence of cardioplegia. In the noncardioplegia groups, 90% of hearts exhibited ischemic contracture (mean time to onset = 24.7 +/- 1.1 minutes), whereas in the cardioplegia groups, only 63% exhibited contracture, and of a significantly delayed onset (37.0 +/- 1.5 min, p less than 0.05). Adult hearts (n = 5) subjected to 30 minutes of normothermic ischemic arrest, in the absence of cardioplegia, recovered 36% +/- 7% of the preischemic left ventricular developed pressure and 37% +/- 9% of the preischemic first derivative of left ventricular pressure on reperfusion; 100% of these hearts exhibited some degree of contracture (mean time to onset = 15.4 +/- 1.1 minutes) by the end of the ischemic period.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Ischemia at the crossroads?

Understanding and controlling the consequences of myocardial ischemia requires us to acknowledge that we are dealing with a complex, dynamic, and highly variable process. The severity and progression of ischemic injury is not solely determined by the extent of oxygen deprivation, but by many other factors, including the accumulation of toxic metabolites. It may not be justified to assume that injury to the myocyte necessarily determines the survival of the organ; other components, such as the endothelium and the conducting system, may play a crucial role. Many factors can influence the severity and evolution of ischemic injury, perhaps the most important being the extent of residual (or collateral) flow to the affected tissue. If the ischemia is relatively mild, then the myocardium may survive for some long time, and drugs and other interventions may be used to further extend this period. However, reperfusion and the establishment of an adequate level of coronary flow is an absolute prerequisite for sustained tissue survival. The more severe the ischemia, the earlier must be the reperfusion. However, reperfusion of previously ischemic tissue is not without hazard, and it may precipitate potentially lethal events such as arrhythmias. Reperfusion may possibly result in the death of cells that were potentially viable in the moments before reflow was established, and there is good evidence that manipulation of reperfusion conditions may accelerate and possibly enhance recovery from ischemia. Much remains to be learned about myocardial ischemia and reperfusion, and in doing this we should perhaps put some of the older, yet well established, concepts behind us.

Coronary Disease↗
PubMed1988

Reperfusion-induced arrhythmias in the isolated rabbit heart: characterization of the influence of the duration of regional ischemia and the extracellular potassium concentration.

The systematic investigation of the genesis and control of arrhythmias during ischemia and reperfusion requires a reproducible preparation in which arrhythmias can be induced with relative ease. The requirements for appropriate statistical analysis often requires that large numbers of animals be studied and hence cost becomes an important factor. The rat offers many advantages but is often criticized on the basis of its atypical action potential and a need exists for an alternative small animal model. The guinea-pig, because of its highly collateralized coronary circulation, cannot be used for the induction of regional ischemia and the rabbit is often dismissed on the grounds that it has a low incidence of arrhythmias. In the present study we have shown that if the perfusion conditions (duration of ischemia and extracellular potassium concentrations) are appropriately selected then the rabbit heart exhibits a high and reproducible susceptibility to reperfusion-induced arrhythmias. Hearts (n = 10 in each group) were subjected to 20 min of regional ischemia induced by coronary artery ligation, the potassium concentration of the perfusate being 2.50, 2.75, 3.00, 3.25, 3.50 or 4.38 mM. A bell-shaped relationship was demonstrated with an optimum susceptibility at 3.00 mM where 60% of the hearts exhibited reperfusion-induced ventricular fibrillation and 80% of the hearts exhibited ventricular tachycardia. With concentration of potassium above 3.00 mM there was a progressive decline in susceptibility (only one out of ten hearts fibrillated when potassium was 4.38 mM). With concentrations of potassium below 3.00 mM there was also a reduction in susceptibility to fibrillation. Using an optimally arrhythmogenic concentration of 3.00 mM potassium, hearts (n = 10 in each group) were subjected to 10, 15, 20, 25, 30 or 40 min of regional ischemia followed by 5 min reperfusion. A bell-shaped time-susceptibility curve was obtained such that with increasing durations of ischemia from 20 to 30 min there was an increasing incidence of reperfusion-induced arrhythmias. Beyond this optimum (at which 60% exhibited reperfusion-induced ventricular fibrillation) there was a decline in the susceptibility of the hearts to fibrillation. Heart rate and coronary flow exhibited no consistent significant relationship with either potassium concentration or duration of regional ischemia. Studies of the time of onset and duration of reperfusion-induced arrhythmias showed that 90% of arrhythmias were initiated within the first 60 s of reperfusion but that the duration was highly variable.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Free radicals and calcium: simultaneous interacting triggers as determinants of vulnerability to reperfusion-induced arrhythmias in the rat heart.

Using the isolated perfused rat heart with regional ischemia and reperfusion, we have two antiarrhythmic interventions (the spin trap agent PBN [N-tert-butyl-alpha-phenylnitrone] and perfusate calcium reduction), administered just before reperfusion, to investigate mechanisms determining the vulnerability of the heart to reperfusion-induced ventricular fibrillation. Hearts were subjected to regional ischemia (5, 10, 20, 30 or 40 min) followed by reperfusion. Four groups were studied for each ischemic time: (i) control hearts with no antiarrhythmic intervention; (ii) hearts perfused with PBN (30 mumol/l) during the final 1 min of ischemia and throughout reperfusion, (iii) hearts perfused with low-calcium buffer (0.4 mmol/l) during the final 1 min of ischemia and throughout reperfusion and (iv) hearts perfused with PBN (30 mumol/l) and low-calcium (0.4 mmol/l) during the final 1 min of ischemia and throughout reperfusion. In control hearts, a bell-shaped time-vulnerability curve was obtained with 0, 91, 67, 33 and 17% of the hearts exhibiting irreversible fibrillation during reperfusion after 5, 10, 20, 30 and 40 min of ischemia, respectively. In the PBN group, the values were 8, 41 (P less than 0.05), 41, 33 and 8%, respectively. In the calcium reduction group the values were 17, 50, 8 (P less than 0.05), 8 and 0, respectively. Thus, PBN caused a significant reduction in reperfusion-induced ventricular fibrillation after 10 min of ischemia but had no significant effect with reperfusion after 20 min of ischemia. In contrast, calcium reduction had no significant effect after 10 min of ischemia but caused a significant reduction after 20 min of ischemia. When PBN treatment with calcium reduction were combined we obtained significant anti-arrhythmic effects after both 10 min (P less than 0.05) and 20 min (P less than 0.05) of ischemia. The additive effects of these two interventions, and the different ischemic-times after which they are most effective, has led us to propose that multiple triggers, each with different underlying mechanisms may be capable of initiating events which lead to ventricular fibrillation.

Animals↗
PubMed1988

The Lambeth Conventions: guidelines for the study of arrhythmias in ischaemia infarction, and reperfusion.

The Lambeth Conventions are guidelines intended to be of practical value in the investigation of arrhythmias induced by ischaemia, infarction, and reperfusion. They cover the design and execution of experiments and the definition, classification, quantification, and analysis of arrhythmias. Investigators are encouraged to adopt the conventions in the hope that this will improve uniformity and interlaboratory comparisons.

Animals↗
PubMed1988

Reperfusion-induced arrhythmias: mechanisms of protection by glucose and mannitol.

Isolated rat hearts (n = 15/group) were subjected to regional ischemia (10 min) and reperfusion (3 min). Mannitol (5, 11, 25, 50, 55, 61, or 75 mM included in the perfusate throughout) reduced reperfusion-induced sustained ventricular fibrillation (VF) from its control incidence of 93% (14/15) to 80, 80, 40, 27, 47, 80, and 80%, respectively. Addition of glucose (11 mM) potentiated this effect, VF now fell to 87, 47, 33, 7, 7, 7, 13, and 13%, respectively. However, 11 mM glucose alone exerted no antiarrhythmic effects. When hearts (n = 15/group) were perfused with identical osmotic loads of mannitol plus glucose (11 + 50, 50 + 11, 61 + 0, or 0 + 61 mM, respectively), very different antiarrhythmic effects were observed. When given throughout the experimental period, glucose alone (0, 11, 25, 50 or 61 mM) had no effect on the incidence of VF (93, 87, 47, 53, and 20%, respectively), but when glucose was added 2 min before reperfusion, improved protection was observed (VF: 93, 87, 40, 27, and 13%, respectively). Our results suggest that the osmotic and free-radical scavenging properties of hexoses are relatively unimportant in relation to their antiarrhythmic effects. The metabolic effects are complex, suggesting that low concentrations of glucose may be beneficial, whereas high concentrations may be detrimental.

Animals↗
PubMed1988

Ischemia- and reperfusion-induced arrhythmias in conscious rats--studies with prazosin and atenolol.

A conscious rat system has been developed to investigate the ability of alpha- and beta-adrenoceptor blocking agents to modify the severity of ischemia- and reperfusion-induced arrhythmias. Ischemia-induced arrhythmias were studied during a 30 min period of occlusion of the left anterior descending (LAD) coronary artery, and 100% of control animals (n = 24) exhibited ventricular tachycardia and 63% ventricular fibrillation. Beta-adrenoceptor blockade with atenolol (1 mg/kg body weight) significantly reduced the incidence of ventricular fibrillation to 17% (p less than 0.05). In contrast, alpha-adrenoceptor blockade with prazosin (0.01, 0.1 or 1 mg/kg body weight) failed to reduce the incidence of arrhythmias and actually increased mortality. This higher mortality with prazosin was associated with bradyarrhythmias. Administration of atenolol (1 mg/kg body weight) also reduced the incidence of reperfusion-induced ventricular fibrillation after a 5 min period of ischemia from 100% to 58% (p less than 0.05). Prazosin could not be tested due to the high mortality during coronary occlusion. Autopsy studies of hearts from the control, atenolol and prazosin groups indicated that all groups had similar occluded zone volumes. In conclusion, in conscious rats beta-blockade with atenolol reduced the incidence of both ischemia- and reperfusion-induced arrhythmias, whereas alpha-blockade with prazosin at the 3 doses studied failed to exert a protective effect and actually increased mortality.

Animals↗
PubMed1988

Evolving myocardial infarction in the rat in vivo: an inappropriate model for the investigation of drug-induced infarct size limitation during sustained regional ischaemia.

Despite the rat heart having very low collateral flow, there are many reports of pharmacological limitation of infarct size in rats with permanent coronary occlusion. Investigating possible artefacts, cardiac function was measured in isolated rat hearts (n = 12/group) 1, 2, 4, 6, 12, 18, 24, or 48 h after permanent coronary occlusion. In sham operated controls, cardiac output was 63.8 +/- 3.8 ml/min; in rats with occlusion this fell to 37.7 +/- 3.3 ml/min after 1 h of occlusion and did not increase during the 48 h of study. Lumen areas, areas of underperfusion, and minimum wall thickness were unchanged after 4 h of occlusion. Between 4 and 12 h, substantial wall thinning occurred (midinfarct wall thickness decreased from 3.69 +/- 0.24 mm to 2.01 +/- 0.16 mm). After 12 h of occlusion, wall thinning and expansion of the infarct increased lumen volume by three- to fourfold. Wall thinning resulted in a progressive decrease in the volume of the zone of underperfusion (which decreased by almost 30% over 48 h). Tetrazolium negative tissue was not evident in the first 4 h of occlusion but by 12 h, 85.0 +/- 2.6% of the underperfused tissue was necrotic. Gross examination of sections often indicated apparently tetrazolium positive tissue within the zone of underperfusion. Microscopic examination of histological sections revealed this tissue to be necrotic but, in contrast to the tetrazolium negative tissue within the zone of underperfusion, not yet subject to white cell infiltration. "Apparent" infarct size limitation in the rat heart might be due to: (1) incorrect designation of tissue as tetrazolium positive within the severely ischaemic zone of underperfusion; (2) inappropriately equating the zone of underperfusion (measured at the end of ischaemia) to the risk zone (measured at the onset of ischaemia); (3) the possibility that some drugs might affect white cell infiltration, tetrazolium staining characteristics, wall thinning, and tissue remodelling.

Animals↗
PubMed1988

Mannitol and reperfusion-induced arrhythmias: possible mechanisms of action in the isolated rat heart.

Mannitol has been shown to exert a dose-dependent, antiarrhythmic effect in the rat heart during reperfusion following a brief period of regional myocardial ischemia. Isolated perfused rat hearts were used to determine whether this protective effect is direct (ie, operative during reperfusion) or indirect (ie, due to an action during ischemia). Hearts (12 in each group) were subjected to 5, 10, 20, 30 or 40 mins of regional ischemia which was induced by ligation of the left anterior descending coronary artery. Upon reperfusion 25%, 100%, 83%, 33% and 17%, respectively, of the hearts fibrillated and 8%, 92%, 58%, 17% and 17% remained in irreversible fibrillation for the duration of the reperfusion period. Addition of mannitol (50 mM, the optimal antiarrhythmic dose) to the perfusion fluid throughout the experiment (early administration) caused a shift of this 'bell-shaped' time-vulnerability curve to the right such that the highest incidence of arrhythmias occurred after 20 mins rather than 10 mins of ischemia. Similar shifts were seen in other indices of electrical instability. Regional ischemia caused a 40 to 45% reduction in coronary flow in all groups of hearts, with no significant difference between the control and the mannitol-treated series. Heart rate fell by a mean of 10 to 15% in all control hearts and by a similar extent in mannitol-treated hearts. In additional studies, mannitol (50 mM) was administered 2 mins before reperfusion and throughout the reperfusion period (late administration studies). In the mannitol-free control group 100% of the hearts exhibited fibrillation and 92% remained in fibrillation for the duration of the reperfusion period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Optimal myocardial protection during crystalloid cardioplegia. Interrelationship between volume and duration of infusion.

There is often a large difference between volumes of crystalloid cardioplegic solution used clinically (2 to 4 ml/gm myocardium) and experimentally (in rat heart preparations, volumes of 30 ml/gm or more are used). In an attempt to reconcile these differences and define the minimum volume and/or duration of infusion of the St. Thomas' Hospital cardioplegic solution consistent with maximal myocardial protection, we have used the isolated working rat heart to characterize the relationships between myocardial protection and (1) the duration of cardioplegic infusion and (2) the volume of cardioplegic infusion. Hearts (n = 6 per group, weighing 0.90 +/- 0.06 gm) were subjected to 0, 5, 10, 15, 30, 45, 60, 120, 180, 240, or 300 seconds of cardioplegic infusion (mean infusion volumes = 0, 1.3 +/- 0.1, 2.0 +/- 0.1, 2.8 +/- 0.2, 5.0 +/- 0.1, 8.3 +/- 0.2, 10.5 +/- 0.8, 21.8 +/- 2.1, 22.7 +/- 1.3, 32.3 +/- 2.1, and 39.1 +/- 1.8 ml per heart, respectively) before 30 minutes of normothermic ischemia. They recovered 3.9% +/- 2.3%, 9.7% +/- 5.0%, 22.8% +/- 5.8%, 34.6% +/- 4.6%, 54.7% +/- 6.6%, 64.0% +/- 5.0%, 67.4% +/- 4.0%, 56.6% +/- 11.1%, 60.0% +/- 5.8%, 51.6% +/- 7.0%, and 68.0% +/- 7.8% of their preischemic cardiac output on reperfusion. Creatine kinase leakage, tissue adenosine triphosphate and creatine phosphate content, and other indices of cardiac function supported this observation. To assess volume of infusion rather than duration, we infused hearts (n = 6 per group) with 1.0, 1.5, or 2.0 ml of cardioplegic solution over 120 seconds. Although recovery of cardiac output with 2.0 ml (56.2% +/- 6.8%) was not significantly different from that (56.6% +/- 11.1%) observed with large volumes of solution (21.9 +/- 2.1 ml), infusion of 1.5 and 1.0 ml resulted in poor recovery of cardiac output (40.1% +/- 4.6% and 21.8% +/- 3.9%, respectively). To assess duration (with low volumes) rather than volume of infusion, we infused hearts (n = 6 per group) with 2.0 ml of cardioplegic solution over 10, 30, 60, or 120 seconds. Maximal protection was observed with 30, 60, and 120 seconds of infusion (recovery of cardiac output = 56.7% +/- 5.9%, 45.1% +/- 7.9%, and 56.2% +/- 6.8%, respectively). Our results suggest that, for maximum myocardial protection, the St. Thomas' Hospital solution should be infused at a rate of not less than 2.0 ml/gm wet weight of heart and that the duration of infusion should be not less than 30 seconds.

Animals↗
PubMed1988

Myocardial salvage with allopurinol during 24 h of permanent coronary occlusion: importance of pretreatment.

Cardioprotection by allopurinol during ischemia is thought to be due to inhibition of xanthine oxidase-derived reactive oxygen intermediates. Previous studies have reported that long pretreatment with allopurinol limits tissue necrosis during acute myocardial ischemia. This study investigated whether a prolonged pretreatment with allopurinol was necessary for cardioprotection. Tissue necrosis was measured in a closed chest canine model of permanent coronary occlusion when the drug was administered post coronary occlusion. In 20 dogs the coronary artery was occluded by an embolus injected into the left coronary artery. Three groups were studied: untreated controls (saline given intravenously post occlusion); allopurinol 1 min post occlusion (25 mg/kg given intravenously, 1 min post occlusion); and allopurinol 30 mins post occlusion (25 mg/kg given intravenously 30 mins post occlusion). Dogs in both drug treatment groups also received allopurinol (25 mg/kg intravenously) every 8 h post coronary occlusion. After 24 h of permanent coronary occlusion tissue necrosis was evaluated using triphenyl tetrazolium chloride staining and was related to major baseline predictors of infarct size, including anatomic risk zone and coronary collateral flow. In control dogs, infarct to risk zone ratio was inversely related to subepicardial collateral flow; analysis of covariance indicated that allopurinol administered post coronary occlusion did not shift this relationship. Treatment with allopurinol within the first minutes after coronary occlusion was ineffective in limiting tissue necrosis in this model of permanent coronary occlusion, therefore, long pretreatment with allopurinol is necessary for cardioprotection.

Allopurinol↗
PubMed1988

Improved myocardial protection by oxygenation of St. Thomas' Hospital cardioplegic solutions. Studies in the rat.

The effect of oxygenation (100% oxygen) of the St. Thomas' Hospital cardioplegic solutions No. 1 (MacCarthy) and No.2 (Plegisol, Abbott Laboratories, North Chicago, Ill.) was examined in the isolated working rat heart subjected to long periods (3 hours for studies with solution No. 1 and 4 hours for studies with solution No. 2) of hypothermic (20 degrees C) ischemic arrest with multidose (every 30 minutes) cardioplegic infusion. At the aortic infusion point the oxygen tension of the oxygenated solutions (measured at 20 degrees C) was in the range of 320 to 560 mm Hg whereas that of the nonoxygenated solutions was less than 150 mm Hg. Twenty hearts (10 oxygenated and 10 nonoxygenated) were studied for each solution. The studies with solution No. 1 demonstrated that oxygenation led to a significant (p less than 0.05) reduction in the incidence of persistent ventricular fibrillation during postischemic reperfusion. Oxygenation of the cardioplegic solution also improved postischemic functional recovery so that the recovery of aortic flow was improved from 18.7% +/- 8.9% (of its preischemic control level) in the nonoxygenated group to 54.6% +/- 6.6% in the oxygenated group (p less than 0.025). Creatine kinase leakage was also significantly reduced from 27.5 +/- 4.8 to 9.9 +/- 0.6 IU/15 min/gm dry weight (p less than 0.005). Studies with solution No. 2 indicated that protection was better than with solution No. 1, even in the absence of oxygenation. A better degree of functional recovery was obtained after 4 hours of arrest with solution No. 2 than that obtained after only 3 hours of arrest with solution No. 1, and persistent ventricular ventricular fibrillation was never observed with solution No. 2. However, despite the superior performance with solution No. 2, further improvements could be obtained by oxygenation, with that time from the onset of reperfusion to the return of regular sinus rhythm being reduced from 55 +/- 8 to 35 +/- 2 seconds (p less than 0.01), postischemic recovery of aortic flow increasing from 59.8% +/- 7.4% to 85.7% +/- 2.5% (p less than 0.005), and creatine kinase leakage being reduced from 38.1 +/- 7.3 to 16.2 +/- 1.5 IU/15 min/gm dry weight (p less than 0.005). It is concluded that oxygenation of the St. Thomas' Hospital cardioplegic solutions improves their ability to protect the heart against long periods of ischemia and that this is manifested by improved postischemic electrical stability, functional recovery, and reduced creatine kinase leakage.

Animals↗
PubMed1988

Reperfusion-induced arrhythmias: characterization studies with the globally ischemic rat heart.

It has previously been demonstrated in the rat heart, in vivo and in vitro, with regional ischemia, that an asymmetric bell-shaped curve defines the relationship between the vulnerability to reperfusion-induced arrhythmias and the duration of the preceding period of ischemia. The present study sought to establish whether a similar relationship occurred with global ischemia and reperfusion. Using rats from three different sources (two British, one North American) it was observed that, when an appropriate duration of ischemia was selected, reperfusion was capable of eliciting a very high incidence (up to 100%) of ventricular fibrillation and ventricular tachycardia. In the first series of studies an asymmetric bell-shaped relationship was observed such that with reperfusion after 5, 10, 20, 25, 28, 30, 33, 37 and 45 mins 0, 8, 8, 8, 50, 58, 83, 33, 33 and 25% of hearts fibrillated, respectively (12 hearts per group). However, upon repeating the studies with groups of rats from other suppliers or different batches from the same supplier, different results were obtained. Thus, in some study groups a very high incidence of arrhythmia was observed with reperfusion after very short (7.5 mins) durations of ischemia and low incidences were sometimes obtained with reperfusion after 30 mins, a time which, in some study groups, elicited a very high (100%) incidence of severe arrhythmias. These results contrast strikingly with those obtained with regional ischemia where a highly reproducible profile for the incidence of arrhythmias is consistently observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗