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M S Marber

Publications and source records attributed to M S Marber.

66 records · Page 4Linked to original sources
PubMed1994

Myocardial protection after whole body heat stress in the rabbit is dependent on metabolic substrate and is related to the amount of the inducible 70-kD heat stress protein.

The aims of this study were to examine the effects of whole body heat stress and subsequent stress protein induction on glycolytic metabolism, mitochondrial metabolism, and calcium handling within the heart. The effect of heat stress on glycolytic and mitochondrial pathways was examined by measuring contractile performance in the presence of glucose and pyruvate, respectively. Calcium handling was assessed using force-interval relationships. Right ventricular papillary muscles taken from heat-stressed and control rabbit hearts were superfused with Kreb's solution containing either glucose or pyruvate and rendered hypoxic for 30 min. After reoxygenation, the greatest recovery of contractile function occurred in the heat-stressed muscles with pyruvate as substrate; there was, however, no difference in the force-interval relationship between the groups. The degree of contractile recovery was related to the content of the inducible 70-kD but not the 65-kD, heat stress protein. This study suggests that heat stress enhances the ability of rabbit papillary muscle to use pyruvate, but not glucose, after reoxygenation, and that the differences seen in contractility may be secondary to induction of the 72-kD stress protein.

Animals↗
PubMed1993

Attenuation by heat stress of a submaximal calcium paradox in the rabbit heart.

Heat stress limits the injury associated with myocardial ischaemia and reperfusion, an effect previously attributed to enhanced endogenous anti-oxidant activity. We examined the influence of heat stress on the calcium paradox, an injury in which oxidant stress is not thought to play a major role. Twenty-four hours following sham or true heat stress, rabbits were re-anaesthetized and hearts either removed for stress protein analysis (n = 8), or Langendorff-perfused (n = 20) and subjected to a calcium paradox. Ten minutes following calcium repletion (Ca2+ = 1.3 mM), left ventricular developed pressure was better preserved in heat stress vs control hearts (38.3 +/- 5.0 vs 18.8 +/- 4.1 mmHg, respectively, P = 0.003) whilst contracture, measured by left ventricular end-diastolic pressure, was diminished (21.6 +/- 4.7 vs 39.9 +/- 5.2 mmHg, respectively, P = 0.02). Creatine phosphokinase release at 1 min was less in heat stress vs control hearts (10.6 +/- 8.6 vs 86.4 +/- 33.7 U/min/g, respectively, P = 0.01). The myocardial content of the 72 kDa stress protein was elevated eight-fold in heat stress vs control hearts (2.8 +/- 0.2 vs 0.4 +/- 0.1 U, respectively, P = 0.01). This study suggests that some portion of the stress protein response represents a form of cardiac adaptation capable of limiting myocyte injury independent of antioxidant mechanisms.

Animals↗
PubMed1993

A single five minute period of rapid atrial pacing fails to limit infarct size in the in situ rabbit heart.

OBJECTIVE: Rapid pacing has been shown to precondition the dog heart against ischaemic dysrhythmia. The aim of this study was to determine whether rapid pacing could also limit infarct size. METHODS: Rabbits (n = 5) were rapidly paced via the left atrium at 420-480 beats.min-1. Five min of rapid pacing and 10 min of recovery in sinus rhythm were followed by 45 min of regional ischaemia and 120 min of reperfusion. Control rabbits (n = 9) were treated identically without prior rapid pacing. Infarct size was determined in both groups using tetrazolium and expressed as a percentage of the area at risk demarcated by fluorescent microspheres. In a separate series of experiments, rapidly paced Langendorff perfused rabbit hearts (n = 9) were used to determine coronary flow under perfusion conditions designed to simulate the in vivo situation during rapid pacing. RESULTS: Rapid pacing caused a fall in systolic pressure from 91.4(SEM 4.5) to 47.0(5.9) mm Hg (p < 0.01) and diastolic pressure from 67.2(2.9) to 23.6(3.2) mm Hg (p < 0.01). Both recovered within 30 s of cessation of pacing. During rapid pacing the action potential duration shortened from 192(13) to 128(5) ms (p = 0.01) and developed electrical alternans (n = 4). Following rapid pacing the ECG showed either ST depression or T wave inversion (n = 4). Despite these profound changes, rapid pacing did not reduce infarct size v control [52.7(4.6)% v 60.8(9.1)% of the area at risk, respectively]. The in vitro experiments estimated that rapid pacing would result in a reduction in coronary flow to 44% of that in sinus rhythm without a significant rise in lactate efflux. CONCLUSIONS: In our model, pretreatment with rapid pacing fails to reduce infarct size. The most likely reason for this is that rapid pacing at a rate of 480 beats.min-1 does not cause myocardial ischaemia of sufficient severity to trigger the preconditioning response.

Action Potentials↗
PubMed1993

Heat stress limits infarct size in the isolated perfused rabbit heart.

OBJECTIVE: Heat stress, with the expression of heat stress proteins, has been shown to protect the rabbit heart in vitro against global ischaemia/reperfusion injury, though no benefit is apparent in an in vivo rabbit model of infarct size. The aim of this study was therefore to investigate this discrepancy and to discover whether heating itself has any effect which could negate the protection derived from myocardial stress protein synthesis. METHODS: (1) To ascertain whether heat stress could limit infarct size in the absence of blood, isolated buffer perfused hearts, with or without prior heat stress, were subjected to 45 min of regional ischaemia and 120 min reperfusion, and the resulting infarct size was expressed as a percentage of the risk area (I/R%). (2) The observations were repeated in an isolated blood perfused heart model in which a support rabbit (heat stressed or control) was used to perfuse the isolated heart. RESULTS: In the buffer perfused heart, prior heat stress reduced I/R from 70.8(SEM 4.4)%, n = 10, in controls to 51.5(5.7)%, n = 12 (p < 0.05). In hearts perfused by support rabbits, prior heat stress reduced I/R [from 34.7(3.7)%, n = 16, to 23.5(3.3)%, n = 15 (p < 0.05)] only when the perfusing rabbit was a control (not heat stressed). If the perfusing rabbit had been heated, I/R was greater in both heat stressed and control hearts [51.9(7.0)% and 44.9(3.3)%, p < 0.05 v control support rabbit]. CONCLUSIONS: Heat stress limits infarct size in this rabbit model. However it appears to have additional adverse effects, probably on the blood, which may override any benefit associated with myocardial stress protein synthesis.

Animals↗
PubMed1993

Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction.

BACKGROUND: To test the hypothesis that the heat shock response is associated with myocardial salvage, the heat stress protein (HSP) content of cardiac tissue was increased by either ischemic or thermal stress. METHODS AND RESULTS: Rabbits were divided into four groups. Ischemic pretreatment (n = 15) comprised four 5-minute episodes of coronary ligation separated by 10 minutes of reperfusion. The corresponding control group (n = 21) underwent surgical preparation without coronary ligation. Thermal pretreatment (n = 16) involved whole-body temperature elevation to 42 degrees C for 15 minutes; corresponding controls (n = 15) were treated with anesthetic alone. Twenty-four hours later, hearts were removed for HSP estimation or infarct size assessment after a 30-minute coronary ligation. Myocardial HSP72 content assessed by Western blotting was elevated by both ischemic and thermal pretreatments (2.5 +/- 0.2 units, n = 4, and 2.8 +/- 0.3 units, n = 4, mean +/- SEM; P = NS, respectively) compared with the corresponding control groups (1.0 +/- 0.3, n = 4, P < or = .01 and 0.3 +/- 0.1, n = 4, P < or = .01, respectively). HSP60 was preferentially elevated by ischemic pretreatment. After a 30-minute coronary occlusion and 120 minutes of reperfusion, ischemic and thermal pretreatments limited infarct size as a percentage of the volume at risk by 28.8 +/- 5.2% vs 52.0 +/- 5.2%, P < or = .01 and 32.8 +/- 3.8% vs 56.9 +/- 6.5%, P < or = .01, respectively. CONCLUSIONS: Myocardial stress protein induced by either sublethal thermal or ischemic injury is associated with myocardial salvage. Our findings suggest that stress protein elevation, rather than the nonspecific effects of thermal or ischemic stress, may be responsible for the myocardial protection seen in this model. Our observations may have important implications regarding myocardial adaptation to brief periods of ischemia.

Animals↗
PubMed1992

The protective role of heat stress in the ischaemic and reperfused rabbit myocardium.

Cells subjected to increases in temperature induce the expression of several proteins known as heat shock or stress proteins. This process enhances the cell's ability to overcome the effects of further stress. In this respect, the effects of heat stress have been reported to protect the hearts of rats following ischaemia and reperfusion. We have confirmed and extended this observation, not only using different indices of myocardial injury but also in another species, namely the rabbit. Animals were anaesthetized and the body temperature raised to 42 degrees C for a 15-min period. Controls were treated in the same way but without heating. Twenty-four hours later the rabbits were re-anaesthetized and the hearts removed for either heat stress protein analysis or perfusion with Krebs buffer using an isolated perfused heart apparatus. Hearts were subjected to 60 min of low flow (1 ml/min) ischaemia followed by 30 min of reperfusion. All hearts subjected to heat stress showed an enhanced recovery of function upon reperfusion as measured by improvements in developed pressure (27.3 +/- 3.6 vs 16.3 +/- 3.0 mmHg) and diastolic pressure (37.3 +/- 7.4 vs 54.7 +/- 3.1 mmHg). In addition, creatine kinase release, associated with reperfusion, was significantly reduced in the heat-stressed hearts (532 +/- 102 vs 1138 +/- 73 mU/min/g wet wt). Myocardial accumulation and release of oxidized glutathione, an index of oxidative stress, was significantly reduced in the heat-stressed group (0.003 +/- 0.003 vs 0.376 +/- 0.113 nmol/min/g wet wt). The improved metabolic status of the reperfused heat-stressed hearts was further demonstrated by a significant conservation in the levels of ATP (6.1 +/- 0.9 vs 2.8 +/- 0.8 mumol/g dry wt) and CP (36.9 +/- 6.4 vs 16.4 +/- 5.1 mumol/g dry wt). Finally, isolated mitochondrial function in terms of respiratory control index (RCI) was maintained in the heat-stressed hearts (9.2 +/- 0.9 vs 5.7 +/- 0.2) and overloading with calcium was reduced. These data extend the hypothesis that heat stress protects the heart following ischaemia and reperfusion in this in vitro model, in a way as yet undetermined.

Adenosine Triphosphate↗
PubMed1992

Transoesophageal echocardiography in the diagnosis of paradoxical embolism.

Two patients with systemic embolism were studied with transoesophageal contrast echocardiography which demonstrated its probable paradoxical nature. In both cases paradoxical embolism was associated with pulmonary embolism. Precordial contrast echocardiography demonstrated a right-to-left shunt in one patient but was unable to demonstrate a shunt in the second. Transoesophageal echocardiography suggested that the shunt was across a patent foramen oval in both cases and revealed large thrombi in the pulmonary arteries in one. When precordial contrast echocardiography reveals a right-to-left shunt or when it is technically inadequate in patients suspected of having one, transoesophageal contrast echocardiography can demonstrate the nature of the shunt and is an alternative to cardiac catheterisation techniques. In addition, it can reveal large thrombi in the pulmonary arteries.

Adolescent↗
PubMed1992

Need for invasive cardiological assessment and intervention: a ten year review.

The uptake of invasive cardiological investigation and cardiopulmonary bypass procedures by the North West Surrey Health District was audited over the years 1979-88. Growth was almost continuous throughout the ten year period. The need within the district each year for coronary angiography seemed to be between 111 and 171 and for surgical revascularisation of the myocardium between 63 and 96 procedures; the first figure is the mean of the second quinquennial period (1984-88) and the second figure the total for 1988. After correction for the standardised mortality ratio and catchment area, the national requirement should lie between 690 and 1070 coronary angiograms and 390 and 600 coronary artery bypass graft operations per million population each year. There is a further national requirement for 70 valvar heart operations and 30 miscellaneous procedures per million population each year. Owing to delays in the provision of services, 20 patients died of a cardiovascular cause while they were on the waiting list for investigation or surgery. In the United Kingdom the annual target to be achieved by 1990 was 300 coronary artery bypass procedures per million population.

Adult↗
PubMedDate not supplied

In vivo myocardial gene transfer: optimization, evaluation and direct comparison of gene transfer vectors.

The purpose was to determine the relative efficiency, toxicity and duration of expression following gene delivery by intramyocardial injection of naked DNA, naked DNA complexed to cationic liposomes, naked DNA complexed to cationic liposomes with integrin-targetting peptide, recombinant (E1-/E3-) adenovirus, recombinant adeno-associated virus and recombinant (ICP27-) herpes simplex virus. All vectors incorporated a LacZ reporter driven by a promoter containing the hCMV-IE promoter/enhancer. Efficiency was scored by counting positive cells in five standard microscopic sections harvested from the left ventricular apex. Rabbit hearts (n = 100) were examined from 2 to 56 days after injection. Uncomplexed and complexed naked DNA were very inefficient with less than one positive cell visible per heart. The viral vectors all resulted in robust gene expression with adenovirus being the most efficient by at least one order of magnitude before 21 days. However, despite disparate titres, the efficiency beyond 21 days of adenovirus and adeno-associated virus were comparable. In contrast to adeno-associated virus, both adenovirus and herpes-simplex virus were associated with a marked inflammatory response. Despite reporter gene activity appearing only after 21 days, adeno-associated virus shows comparative promise as a myocardial gene delivery vector.

Adenoviridae↗
PubMedDate not supplied

The open artery hypothesis: potential mechanisms of action.

The postinfarction period is one of intense dynamic activity because the cardiovascular system undergoes a number of adaptive responses attempting to maintain cardiac output. These homeostatic responses contribute to the processes involved in postinfarction ventricular remodeling and involve acute, chronic, systemic, and local reactions. Almost immediately, neurohormones are activated that alter hemodynamic load, and, later, stimulate myocyte hypertrophy, while locally, inflammatory processes clear necrotic debris, reorganize the extracellular matrix, and orchestrate scar formation. Where the initial cardiac insult is sufficiently large (eg, necrosis of more than 40% of left ventricular mass), remodeling responses are exaggerated and may become maladaptive, contributing to the poor long-term prognosis associated with myocardial infarction. Although several studies have shown clear benefits after neurohormonal modulation and/or manipulation of ventricular loading forces in the postinfarction setting, relatively few studies have investigated the potential merits of a patent infarct-related artery during postinfarction ventricular remodeling. In particular, the salutary effects of late revascularization of previously occluded vessels remains controversial. Thus, though this issue remains speculative, our present practice must be governed by circumstantial evidence and hypothetical arguments. This article discusses the potential mechanisms whereby late reperfusion of an infarcted myocardial region may benefit long-term prognosis.

Animals↗