Abrupt rate accelerations or premature beats cause life-threatening arrhythmias in mice with long-QT3 syndrome.

Deletion of amino-acid residues 1505-1507 (KPQ) in the cardiac SCN5A Na(+) channel causes autosomal dominant prolongation of the electrocardiographic QT interval (long-QT syndrome type 3 or LQT3). Excessive prolongation of the action potential at low heart rates predisposes individuals with LQT3 to fatal arrhythmias, typically at rest or during sleep. Here we report that mice heterozygous for a knock-in KPQ-deletion (SCN5A(Delta/+)) show the essential LQT3 features and spontaneously develop life-threatening polymorphous ventricular arrhythmias. Unexpectedly, sudden accelerations in heart rate or premature beats caused lengthening of the action potential with early afterdepolarization and triggered arrhythmias in Scn5a(Delta/+) mice. Adrenergic agonists normalized the response to rate acceleration in vitro and suppressed arrhythmias upon premature stimulation in vivo. These results show the possible risk of sudden heart-rate accelerations. The Scn5a(Delta/+) mouse with its predisposition for pacing-induced arrhythmia might be useful for the development of new treatments for the LQT3 syndrome.

Lack of the effect of superoxide dismutase and catalase on Na+,K+-ATPase activity in stunned rabbit hearts.

Reactive oxygen species (ROS) have been implicated in the mechanism of postischemic contractile dysfunction, known as myocardial stunning. In this study, we examined protective effects of antioxidant enzymes, superoxide dismutase (SOD) and catalase, against ischemia/reperfusion-induced cardiac dysfunction and inhibition of Na+,K+-ATPase activity. Isolated Langendorff-perfused rabbit hearts were subjected to 15 min of global normothermic ischemia followed by 10 min reperfusion. The hearts treated with SOD plus catalase did not show significant recovery of left ventricular (LV) end-diastolic pressure compared with untreated ischemic reperfused hearts. Treatment with antioxidants had no protective effects on developed LV pressure or its maximal positive and negative first derivatives (+/-LVdP/dt). Myocardial stunning was accompanied by significant loss in sarcolemmal Na+,K+-ATPase activity and thiol group content. Inhibition of enzyme activity and oxidation of SH groups were not prevented by antioxidant enzymes. These results suggest that administration of SOD and catalase in perfusate do not protect significantly against cardiac dysfunction in stunned rabbit myocardium.

[The effect of type II diabetes and the metabolic syndrome on cardiac second window preconditioning]. / Het effect van type ii diabetes en het metabool syndroom op cardiale tweede venster preconditionering.

Preconditioning is the most powerful endogenous mechanism, to protect the heart against ischemic damage. Conflicting data are published whether preconditioning can be induced in case of diabetes and the metabolic syndrome, which are clinically very relevant conditions. If preconditioning could be induced consistently and chronically in this population, an important reduction of surgical morbidity and mortality could be reached. In this project we induced hypoxic preconditioning in mice and used cardiac pressure-conductance catheterisation and infarct size as outcome parameters. In the first part, we found that hypoxic preconditioning was capable to reduce infarct size with 40% and preserve the load-independent parameters with 33% after coronary occlusion. A DKO (double knock-out: ob/ob; LDLR-/-) model for the metabolic syndrome developed a larger infarct size and had a reduced contractility. No preconditioning could be induced in this model. To detect the determing factor of the resistance to preconditioning, we used single knock-out models. A comparable preconditioning effect of wild type mice could be induced in the lipoprotein receptor deficient (LDLR-/-) model for dyslipidemia. The leptin deficient (ob/ob) model, characterized by insulin resistance and abdominal obesity had, identically to the DKO model, a larger infarct size. A second window of preconditioning could be induced, although it was less pronounced than the wild type and LDLR-/- model. Insulin resistance and abdominal obesity could be identified as the major factor in the resistance to preconditioning.

Coronary thrombolysis and infarct size reduction after intravenous infusion of recombinant tissue-type plasminogen activator in nonhuman primates.

Occlusive thrombus was produced by thrombin-induced coagulation in the left anterior descending coronary artery (LAD) of 16 open-chest baboons. In six control animals, occlusive thrombosis persisting over a period of 4 h as evidenced by coronary arteriography resulted in large transmural infarction (63.1 +/- 3.5% of the perfusion area). In 10 animals, tissue-type plasminogen activator obtained by recombinant DNA technology (rt-PA) was infused systemically at a rate of 1,000 IU (10 micrograms)/kg per min for 30 min after 30-80 min of coronary thrombosis. Reperfusion occurred within 30 min in nine animals. In one animal, intravenous infusion was followed by an intracoronary infusion at the same rate, which resulted in thrombolysis within 8 min. In the rt-PA group, mean duration of occlusion before reperfusion was 77 +/- 24 min. Reocclusion occurred in one animal. Recanalization resulted in an overall reduction of infarct size (37.8 +/- 5.9%, P less than 0.05 versus controls). Residual infarction was related to the duration of occlusion (r = 0.80, P less than 0.01). Reperfusion was associated with reduced reflow. Myocardial blood flow in the perfusion area of the LAD was only 70% of normal after 4 h despite perfect angiographic refilling. The infusion of rt-PA was not associated with systemic activation of the fibrinolytic system, fibrinogen breakdown, or clinically evident bleeding. It is concluded that intravenous infusion of rt-PA may recanalize thrombosed coronary vessels without inducing systemic lysis. The extent of residual infarction is closely related to the duration of coronary artery occlusion before thrombolysis.

Response to exercise and mechanical efficiency in non-ischaemic stunning, induced by short-term rapid pacing in dogs: a role for calcium?

AIM: Rapid pacing (RP) is a regularly used model to induce heart failure in dogs. The aim of the study was to evaluate Ca2+ handling, left ventricular (LV) contractile response during Ca2+ administration compared to exercise, as well as oxygen consumption and mechanical efficiency after 48 h of RP. METHODS: Fifty-three mongrel dogs were instrumented to measure LV pressure, LV fractional shortening, regional wall thickening and coronary blood flow. Contractile reserve was measured with isoproterenol and intravenous (IV) Ca2+ administration. To assess the function of the sarcoplasmic reticulum (SR), post-extrasystolic potentiation (PESP) and SR Ca2+ uptake were measured. A graded treadmill test was performed in baseline and after RP (n = 14). In a separate group of animals (n = 5), myocardial performance and oxygen consumption were measured using a wide range of loading conditions. RESULTS: Left ventricular contractility was significantly decreased upon cessation of pacing. The contractile response to isoproterenol was blunted compared to a preserved response to IV Ca2+ . Post-extrasystolic potentiation was slightly increased after RP. Maximal velocity (Vmax ) of SR Ca2+ uptake was unchanged. Contractile response during exercise is attenuated after RP. External work is reduced, whereas oxygen consumption is preserved, provoking a reduced mechanical efficiency. CONCLUSION: Forty-eight-hours RP provokes a reversible LV dysfunction, while the SR function and response to exogenous Ca2+ are preserved. This is compatible with an intracellular functional remodelling to counteract Ca2+ overload provoked by RP. Left ventricular dysfunction is accompanied by a reduced contractile reserve, but an unchanged oxygen consumption, illustrating an alteration in oxygen utilization.

Serum-myocardium gradients of non-esterified fatty acids in dog, rat and man.

In the three species under investigation (dog, rat and man) a gradient from serum to heart tissue for total non-esterified fatty acids was assessed. The ratios serum/left ventricular tissue in dogs, serum/right auricular appendage in dogs, serum/whole heart tissue in rats and serum/right auricular appendage in man were found to be 6.4, 2.5, 5.6 and 2.8, respectively. The highest gradient was found for oleic acid, whereas no significant gradient for arachidonic acid could be detected. In the dog the arterio:local venous differences of non-esterified fatty acids across the left ventricular tissue correlated better with the serum/tissue ratio of non-esterified fatty acids than with the arterial non-esterified fatty acid level. Since the correlation coefficient (0.74) was still far from excellent, more factors than the non-esterified fatty acid serum/tissue gradient are likely to be involved in determining the extent to which non-esterified fatty acids are extracted by myocardial tissue.

ALCAPA syndrome: an example of chronic myocardial hypoperfusion?

OBJECTIVES: The purpose of this study was to evaluate functional variables and morphologic correlates of chronically hypoperfused myocardium before and after revascularization. BACKGROUND: Neonates with congenital anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA syndrome) develop some myocardial necrosis shortly after birth. The survivors of this event are left with a localized infarction and an almost entirely collateral circulation-dependent perfusion of the left ventricle that results in poor global left ventricular function. Survival beyond infancy is uncommon because of severe left heart failure. Revascularization, however, brings about functional recovery with good clinical outcome. The ALCAPA syndrome is thus characterized by chronic collateral circulation-dependent low perfusion, low contraction matching and potential revivability. METHODS: Five patients with ALCAPA syndrome are presented, with preoperative and postoperative clinical findings and histologic data obtained from intraoperative transmural biopsy specimens. RESULTS: The angiographically assessed preoperative ejection fraction was 33 +/- 19% (mean +/- SD). Postoperative echocardiographic follow-up revealed normal left ventricular function in all patients. Histologic study of the biopsy specimens taken from the region perfused by the anomalous artery showed a variable degree of fibrosis (51 +/- 32%). The ultrastructure of the remaining myocytes revealed viable characteristics, but a substantial percent (46 +/- 26%) showed a markedly reduced fraction of contractile material. CONCLUSIONS: These ultrastructural studies suggest delayed subcellular adaptive responses in the chronically hypoperfused myocardium of patients with ALCAPA syndrome.

Repeated stunning precedes myocardial hibernation in progressive multiple coronary artery obstruction.

OBJECTIVE: The aim of this study was to characterize a regional myocardial flow-function relationship in collateral dependent myocardium produced by multiple coronary artery obstruction. METHODS: Ameroid constrictors were placed around the proximal right (RC) and circumflex (CX) coronary arteries and a silicon tubing cuff around the proximal LAD (left anterior descending artery) (luminal stenosis +/- 77%) in 18 dogs. Weekly two-dimensional echocardiography was performed for regional function (anterior [A], inferoposterior [IP], wall thickening [WT]), and fractional shortening (FS). Colored microspheres injected at baseline and before sacrifice, before and after dipyridamole (0.5 mg/kg) injection, determined resting flow (RF) and coronary reserve (CR), respectively. RESULTS: Coronary angiography performed at four weeks after surgery confirmed occlusion of RC and CX with collateralization and a tight stenosis of LAD. Initially, an episodic reduction in A and IP WT was observed which became persistent later (AWT: 16 +/- 3%; IPWT: 16 +/- 4%, FS: 20 +/- 4%, p < 0.005 vs. baseline [BS]). With dobutamine a biphasic response (improvement in A and IP WT between 5-15 and dysfunction between 20-30 microg/kg/min) was observed. Seven dogs were sacrificed at eight weeks and showed normal RF but reduced transmural CR (A: 75 +/- 18%; IP: 46 +/- 22% of control). Seven dogs underwent PTCA of the LAD at eight weeks and showed gradual improvement in AWT with normalization at 12 weeks (AWT: 30 +/- 5%, p < 0.001 vs. eight weeks). At sacrifice RF and CR in the A wall were normal but there was reduced subendocardial RF in the IP region (64% of BS). Further, biopsy samples showed normal histological findings and high energy phosphate content in all dogs. Radioligand binding assays using 125I-iodocyanopindolol showed downregulation of beta-adrenergic receptor density in the dysfunctional regions compared with control. CONCLUSIONS: In this canine model of viable, collateral dependent and reversibly dysfunctional myocardium, there was early episodic dysfunction followed by persistent dysfunction which was initially associated with normal RF and later with subendocardial hypoperfusion.

Effect of superoxide dismutase on infarct size and postischemic recovery of myocardial contractility and metabolism in dogs.

The effects of superoxide dismutase treatment on infarct size, postischemic recovery of contractile function and tissue content of high energy phosphates were examined in a canine model of myocardial ischemia and reperfusion. Ischemia was induced by thrombotic occlusion of a coronary artery and reperfusion was achieved by intravenous thrombolysis. Average duration of ischemia was 90 min. Fifty closed chest anesthetized dogs were randomized to receive either superoxide dismutase (34,000 IU/min intravenously) or placebo, starting approximately 30 min before and continuing for 30 min into the reperfusion phase. Left ventricular ejection fraction and regional segmental shortening of the postischemic area were calculated from contrast angiograms after 4 h, 48 h and 1 week of reperfusion. Tissue content of high energy phosphates was determined from transmural biopsy after 4 h and 1 week. Infarct size was measured by planimetry of dye-stained heart slices. In the superoxide dismutase and placebo-treated groups, respectively, the mortality rate was 25% and 16%, collateral flow 20 +/- 10 and 23 +/- 18 ml/min per 100 g, area at risk 25 +/- 6% and 26 +/- 7% of the left ventricle and infarct size 28 +/- 19% and 36 +/- 27% of the area at risk. Multiple regression analysis failed to show any beneficial effect of superoxide dismutase treatment on infarct size. Left ventricular ejection fraction, regional segmental shortening of the postischemic area and tissue content of high energy phosphates recovered to a similar extent and at a similar rate in both treated and placebo groups up to 1 week after reperfusion. Thus, in this model of coronary occlusion and reperfusion superoxide dismutase treatment is of no benefit.

Relation between coronary artery stenosis and myocardial purine metabolism, histology and regional function in humans.

In 54 patients undergoing elective or emergency aortocoronary bypass grafting, angiographic and electrocardiographic changes were studied. Five patients with unstable angina and five patients with evolving myocardial infarction were included. High energy phosphate metabolism and the histologic appearance of the myocardium were analyzed in transmural biopsy specimens acquired at the time of surgery. In patients without anterior infarction on the electrocardiogram, severe stenosis of the left anterior descending coronary artery resulted in a reduction of anterior wall motion that was associated with a partial depletion of the adenylate pool. Mitochondrial function, however, remained intact: the adenosine diphosphate/adenosine triphosphate ratio, the energy charge and the creatine phosphate/adenosine triphosphate ratio were in the normal range. Histologic assessment demonstrated viable myocardium with a high incidence of atrophic cells. In evolving myocardial infarction, 170 minutes of acute coronary artery obstruction resulted in anterior wall akinesia associated with a decrease of the sum of the adenylates to 52% and of creatine phosphate to 16% of their normal value (p less than 0.05). The nucleosides accumulated; their major fraction (91%) was inosine. The adenosine diphosphate/adenosine triphosphate ratio increased from 0.14 +/- 0.04 to 0.49 +/- 0.20 (p less than 0.01) and the energy charge decreased from 0.924 +/- 0.021 to 0.660 +/- 0.169 (p less than 0.01). Ultrastructure examination revealed irreversible cell damage in at least the subendocardial layer. These results suggest that the energetic base of reduced contractility due to severe coronary artery stenosis is different from that in acute coronary obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Early intravenous administration of metoprolol enhances myocardial salvage by thrombolysis with recombinant tissue-type plasminogen activator after thrombotic coronary artery occlusion in the dog by improvement of the collateral blood flow to the area at risk.

OBJECTIVES: We studied the effects of beta 1-adrenergic blockade preceding thrombolysis on hemodynamic variables, myocardial blood flow and infarct size in a canine model of thrombotic occlusion of the left anterior descending coronary artery. BACKGROUND: Previous work suggested a reduction in infarct size and improvement in left ventricular function by intravenous beta-blockade preceding thrombolysis. METHODS: Experiments were conducted in 34 anesthetized dogs; 17 received 0.975 mg/kg body weight of metoprolol intravenously starting 15 min after occlusion, and thrombolysis was initiated 60 min after occlusion. Seventeen dogs received saline solution followed by thrombolysis. Coronary blood flow was measured by radioactive microspheres, infarct size by a dye method, hemodynamic variables by catheter-tipped pressure transducers and cardiac output by the thermodilution method. RESULTS: Infarct size in metoprolol- and placebo-treated dogs was 23.62 +/- 18.04% and 41.50 +/- 16.03% of area at risk, respectively (p < 0.01). Before occlusion, myocardial blood flow and hemodynamic variables were similar. Sixty minutes after occlusion, cardiac output (1.94 +/- 0.41 vs. 2.32 +/- 0.68 liters/min, p < 0.01) was lower in the metoprolol-treated dogs. Collateral flow to the area at risk (17.27 +/- 7.44 vs. 10.25 +/- 5.33) and to its epicardial (21.68 +/- 8.04 vs. 11.5 +/- 6.10), midmyocardial (14.30 +/- 8.63 vs. 7.35 +/- 4.94) and endocardial (13.18 +/- 8.21 vs. 6.26 +/- 5.34 cm3/min per 100 g) layers was higher (p < or = 0.05) in the metoprolol-treated dogs. The ratio of epicardial flow area at risk/circumflex territory was inversely correlated to infarct size (r = -0.69, p < 0.01). After 5 min of occlusion, collateral flow was comparable in the five dogs of each group; over the next 55 min it remained constant in the metoprolol group but decreased in the placebo dogs. CONCLUSIONS: Intravenous metoprolol, administered before thrombolysis, enhances infarct size limitation, partly by improvement of collateral flow to area at risk.

Coronary thrombolysis by intravenous infusion of recombinant single chain urokinase-type plasminogen activator or recombinant urokinase in baboons: effect on regional blood flow, infarct size and hemostasis.

An occlusive thrombus was produced by thrombin-induced coagulation in the left anterior descending coronary artery of 18 open chest baboons. In six control animals, occlusive thrombosis persisting for 4 hours resulted in a large transmural infarct (66 +/- 4% of the perfusion area, mean +/- SEM). In six animals, single chain urokinase-type plasminogen activator, obtained by recombinant deoxyribonucleic acid (DNA) technology, was infused intravenously at a rate of 20 micrograms/kg per min for 60 minutes after approximately 45 minutes of coronary thrombosis. Persistent reperfusion occurred within 21 +/- 4 minutes (mean +/- SD). The mean duration of occlusion before reperfusion was 72 +/- 6 minutes. Recanalization resulted in a reduction of infarct size (42 +/- 4%, p less than 0.01 versus control animals). Myocardial blood flow in the perfusion area of the left anterior descending coronary artery was 107% of normal 2.5 hours after recanalization. The infusion of recombinant single chain urokinase-type plasminogen activator was not associated with systemic activation of the fibrinolytic system, fibrinogen breakdown or evident bleeding. In six baboons recombinant low molecular weight urokinase (molecular weight 33,000) was infused intravenously at a rate of 20 micrograms/kg per min for 60 minutes after approximately 45 minutes of coronary thrombosis. Persistent reperfusion occurred within 14 +/- 5 minutes (p less than 0.05 versus recombinant single chain urokinase-type plasminogen activator). The mean duration of occlusion was 69 +/- 14 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of myocardial viability in chronic coronary artery disease using technetium-99m sestamibi SPECT. Correlation with histologic and positron emission tomographic studies and functional follow-up.

OBJECTIVES: The value of 99mTc-sestamibi (2-methoxy-isobutyl isonitrile [MIBI]) as a viability tracer was investigated in patients undergoing coronary artery bypass graft surgery. BACKGROUND: Initial studies claim that rest MIBI single-photon emission computed tomographic (SPECT) studies can be used to assess myocardial viability. METHODS: Thirty patients with a severely stenosed left anterior descending coronary artery and wall motion abnormalities were prospectively included. The patients underwent a MIBI rest study, a positron emission tomographic (PET) flow (13NH3) and metabolism (18F-deoxyglucose) study and nuclear angiography before undergoing bypass surgery. A preoperative transmural biopsy specimen was taken from the left ventricular anterior wall. Morphometry was performed to assess percent fibrosis. After 3 months, radionuclide angiography was repeated. RESULTS: Statistically significant higher MIBI values were found in the group with myocardial viability as assessed by PET than in the group with PET-assessed nonviability (p < 0.01). Significantly higher MIBI values were found in the group with enhanced contractility at 3 months (76 +/- 13% vs. 53 +/- 22%, p < 0.01). A linear relation was found between MIBI uptake and percent fibrosis in the biopsy specimen (r = 0.78, p < 0.00001). When maximizing the threshold for assessment of viability with MIBI by using functional improvement as the reference standard, a cutoff value of 50% was found, with positive and negative predictive values of 82% and 78%, respectively. CONCLUSIONS: 99mTc MIBI uptake was significantly higher in PET-assessed viable areas and in regions with enhanced contractility at 3 months. A linear relation was found between percent fibrosis and MIBI uptake. An optimal threshold of 50% was found for prediction of functional recovery.

Effect of ischemia and reperfusion on protein oxidation in isolated rabbit hearts.

Reactive oxygen species and other oxidants are involved in the mechanism of postischemic contractile dysfunction, known as myocardial stunning. The present study investigated the oxidative modification of cardiac proteins in isolated Langendorff-perfused rabbit hearts subjected to 15 min normothermic ischemia followed by 10 min reperfusion. Reperfusion under these conditions resulted in only 61.8+/-2.7 % recovery of developed pressure relative to preischemic values and this mechanical dysfunction was accompanied by oxidative damage to cardiac proteins. The total sulfhydryl group content was significantly reduced in both ventricle homogenates and mitochondria isolated from stunned hearts. Fluorescence measurements revealed enhanced formation of bityrosines and conjugates of lipid peroxidation-end products with proteins in cardiac homogenates, whereas these parameters were unchanged in the mitochondrial fraction. Reperfusion did not alter protein surface hydrophobicity, as detected by a fluorescent probe 1-anilino-8-naphthalenesulfonate. Our results indicate that oxidation of proteins in mitochondria and possibly in other intracellular structures occurs during cardiac reperfusion and might contribute to ischemia-reperfusion injury.

Dehiscence of a valved conduit in the ascending aorta following low-velocity blunt chest trauma: case report.

We report a case of a 56-year old man presenting with dehiscence of a valved conduit in the ascending aorta following low-velocity blunt thoracic trauma. The patient had a history of a Bentall procedure in 1994. Two weeks before referral to our hospital, the patient fell during a bicycle ride and hit the handlebars of the bicycle with his chest. During the days following the accident, the patient developed progressively worsening fatigue, shortness of breath, and intolerance for even minor physical effort. The presence of an enlarged ascending aorta surrounding the implanted valved graft was confirmed, and the patient was referred to our department for surgical repair, after which the patient had an uneventful recovery and was discharged home on postoperative day 12.

The effect of brain death on cardiovascular function in rats. Part II. The cause of the in vivo haemodynamic changes.

OBJECTIVE: Brain death-induced haemodynamic collapse in rats is not caused by intrinsic myocardial damage as shown in the accompanying paper. We investigated whether this collapse could be caused by the withdrawal of the basal adrenergic tone. METHODS: Heart rate and blood pressure variability was studied in rats before and after brain death. The effect of high doses of phentolamine, propranolol or their combination administered before or after brain death was assessed. RESULTS: Heart rate variability in the respiratory frequency range significantly increased, whereas in the low-frequency range it tended to decrease after brain death. Systolic and diastolic blood pressure variability up to 0.18 Hz largely disappeared, but stayed unchanged in the respiratory frequency range. High-dose combined phentolamine and propranolol pretreatment induced a haemodynamic picture comparable to the situation seen after brain death without pharmacological intervention. Brain death did not further deteriorate the haemodynamic situation after combined pretreatment. On the other hand, once the haemodynamic collapse after brain death had settled, adrenergic blockade had no important influence any more. CONCLUSION: We conclude that the haemodynamic situation seen after brain death is one of profound sympathetic withdrawal.

Adenosine, adenosine receptors and myocardial protection: an updated overview.

Adenosine (Ado) accumulates in tissues under metabolic stress. On myocardial cells, the nucleoside interacts with various receptor subtypes (A(1), A(3), and probably A(2A) and A(2B)) that are coupled, via G proteins, to multiple effectors, including enzymes, channels, transporters and cytoskeletal components. Studies using Ado receptor agonists and antagonists, as well as animals overexpressing the A(1) receptor indicate that Ado exerts anti-ischemic action. Ado released during preconditioning (PC) by short periods of ischemia followed by reperfusion induces cardioprotection to a subsequent sustained ischemia. This protective action is mediated by A(1) and A(3) receptor subtypes and involves the activation and translocation of PKC to sarcolemmal and to mitochondrial membranes. PKC activation leads to an increased opening of ATP-sensitive K(+) (K(ATP)) channels. Recent studies implicate mitochondrial rather than sarcolemmal K(ATP) channels in the protective action of PC. Other effectors possibly contributing to cardioprotection by Ado or PC, and which seem particularly involved in the delayed (second window of) protection, include MAP kinases, heat shock proteins and iNOS. Because of its anti-ischemic effects, Ado has been tested as a protective agent in clinical interventions such as PTCA, CABG and tissue preservation, and was found in most cases to enhance the post-ischemic recovery of function. The mechanisms underlying the role of Ado and of mitochondrial function in PC are not completely clear, and uncertainties remain concerning the role played by newly identified potential effectors such as free radicals, the sarcoplasmic reticulum, etc. In addition, more studies are needed to clarify the signalling mechanisms by which A(3) receptor activation or overexpression may promote apoptosis and cellular injury, as reported by a few recent studies.

Studies on experimental myocardial infarction: dogs or baboons?

The extrapolation to humans of results obtained in experimental studies is a major problem in cardiovascular research. It is generally believed that non-human primates provide a better model for the study of experimental myocardial infarction than the canine or porcine heart. In the present study the transmural distribution of myocardial infarction and collateral flow were compared between dogs and baboons. In the open chest model, the left anterior descending coronary artery was ligated for 4 h. In the subepicardial and subendocardial portions of the left ventricle myocardial blood flow was measured with tracer microspheres, and infarct size and site were determined using triphenyl tetrazolium chloride. In baboons, mean(SD) subendocardial collateral flow was higher than subepicardial collateral flow (41.8(24.6) ml . min-1 X 100 g-1 vs 28.6(21.3) ml . min-1 X 100 g-1 (p less than 0.05)). Subendocardial infarct size (expressed as a percentage of the perfusion area) was smaller than subepicardial infarct size (50.3(8.5)% vs 61.2(9.6)% (p less than 0.001)). In dogs, subendocardial collateral flow was less than subepicardial collateral flow (10.2(6.0) ml . min-1 vs 13.6(4.6) ml . min-1 X 100 g-1 (p less than 0.05)), and subendocardial infarct size was greater than subepicardial infarct size (67.3(12.9)% vs 38.3(18.0)% (p less than 0.01)). When, irrespective of the species or transmural localisation, infarct size is related to collateral flow, expressed as a percentage of normal flow, a weak but significant correlation is obtained (r = 0.61, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)