Ocular fixation to nasal periosteum with a superior oblique tendon in patients with third nerve palsy.

PURPOSE: To report a new surgical approach that uses ocular fixation to the nasal periosteum with superior oblique tendon for patients with complete third nerve palsy. METHODS: Prospective study of 15 patients with complete third nerve palsy who underwent surgery using a superior oblique tenectomy and ocular fixation to the nasal periosteum with the superior oblique tendon fragment. RESULTS: Eleven (73%) patients achieved good ocular alignment, 1 (7%) patient had a cosmetically acceptable result, and 3 (20%) patients had a cosmetically unacceptable result. Five (30%) patients had preoperative diplopia; all achieved resolution of their double vision in the primary position of gaze after surgery. Two patients without preoperative diplopia did not achieve good alignment and had diplopia postoperatively. Follow-up ranged from 8-41 months (mean: 19 months). No operative complications occurred. CONCLUSION: Ocular fixation to the nasal periosteum with superior oblique tendon is a safe, effective, and technically undemanding option for the surgical management of patients with complete third nerve palsy.

Dynamic intracoronary thrombosis does not cause significant downstream platelet embolization.

OBJECTIVE: A mural intracoronary thrombus is a potential source of platelet emboli that may obstruct downstream microvessels, but this phenomenon has not been characterized. The present study aimed to assess the magnitude of myocardial platelet accumulation downstream of a mural intracoronary thrombus and its modification by a concomitant transient coronary occlusion (OC) or by treatment with aspirin. METHODS: The myocardial content of 99mTc-labelled platelets was analyzed in 26 pigs submitted to intimal injury of the left anterior descending coronary artery (LAD) followed by no intervention (n=6), 25-min OC (n=6), or 48-min OC preceded (n=8) or not (n=6) by intravenous administration of 250 mg aspirin. RESULTS: After 2 h, 24 animals had had 12+/-1 cyclic flow reductions (CFRs) reflecting dynamic LAD thrombosis. Myocardial platelet content in the inferior region was similar among groups. Platelet content in the LAD region was not significantly different to that in the inferior region (129+/-19%, P=NS) in the no intervention group, but was increased following OC (172+/-20 and 312+/-71% after 25- and 48-min OC, respectively, P<0.05). Pre-treatment with aspirin lessened the number of CFRs but did not reduce platelet accumulation in LAD myocardium (483+/-148%). Myocardial platelet accumulation was not associated with the magnitude of platelet deposition in the LAD nor with the number of CFRs, but was correlated with myeloperoxidase activity (r=0.91, P<0.001) and with infarct size (r=0.52, P=0.05). Histological analysis frequently showed sparse platelets or small platelet or leukoplatelet aggregates in small vessels, but arteriolar emboli were rare. In none of seven additional experiments coronary angiography showed obstructions of arterial branches during CFRs. CONCLUSION: The magnitude of platelet embolization from a mural intracoronary thrombus into downstream myocardium is small despite the presence of repetitive CFRs.

Splenic involvement by blastic mantle cell lymphoma (large cell/anaplastic variant) mimicking splenic marginal zone lymphoma.

The most cases of splenic marginal zone lymphoma (SMZL) seem to respond favorably to splenectomy. The diagnosis of this lymphoma is mainly based on the recognition of a micronodular pattern of splenic involvement with marginal zone differentiation. However, it is possible to find so-called "marginal zone differentiation" in splenic involvement by other small B-cell lymphomas, particularly mantle cell lymphoma (MCL) and follicular lymphoma. We report a case of blastic MCL, large cell/anaplastic variant with a high level of clinical aggressiveness, showing biphasic cytology and a micronodular pattern which resembles SMZL. A single biopsy corresponding to this case shows two phases of tumoral progression in a MCL, a rare finding in MCL. In conclusion, the differential diagnosis of SMZL must take the possibility of a blastic MCL with biphasic cytology into account, as the case here.

Regional expansion during myocardial ischemia predicts ventricular fibrillation and coronary reocclusion.

Primary ventricular fibrillation (VF) complicating acute myocardial infarction is associated with occluded infarction-related arteries. The relationship between VF during ischemia and spontaneous coronary reocclusion was analyzed in 48 anesthetized pigs submitted to 48 min of coronary ligation and 6 h of reflow. Reocclusion was associated with ischemic VF (6 of 11 animals with VF but only 6 of 37 without it had reocclusion) but not with reperfusion arrhythmias, the size of the ischemic area, the magnitude of electrocardiogram changes or contractile dysfunction during ischemia, or the severity of intimal injury at the occlusion site. The increase in end-diastolic length in the ischemic region during coronary occlusion was associated with ischemic VF (15 min after occlusion, end-diastolic length was 116 +/- 2 and 111 +/- 1% of baseline in animals with or without presenting subsequent VF, respectively) and was retained by multiple logistic regression analysis as the only independent predictor of ischemic VF and reocclusion. Thus ischemic VF is strongly associated with an increased rate of spontaneous coronary reocclusion during subsequent reperfusion. Acute expansion of ischemic myocardium appears as a prominent determinant of both ischemic VF and reocclusion.

Gap junction uncoupler heptanol prevents cell-to-cell progression of hypercontracture and limits necrosis during myocardial reperfusion.

BACKGROUND: The objective of this study was to test the hypothesis that chemical interaction through gap junctions may result in cell-to-cell progression of hypercontracture and that this phenomenon contributes to the final extent of reperfused infarcts. METHODS AND RESULTS: Cell-to-cell transmission of hypercontracture was studied in pairs of freshly isolated adult rat cardiomyocytes. Hypercontracture induced by microinjection of a solution containing 1 mmol/L Ca2+ and 2% lucifer yellow (LY) was transmitted to the adjacent cell (11 of 11 pairs), and the gap junction uncoupler heptanol (2 mmol/L) prevented transmission in 6 of 8 pairs (P=.003), with a perfect association between passage of the LY and transmission of hypercontracture. In the isolated, perfused rat heart submitted to 30 minutes of hypoxia, addition of heptanol to the perfusion media during the first 15 minutes of reoxygenation had a dose-related protective effect against the oxygen paradox, as demonstrated by a reduction of diastolic pressure and marked recovery of developed pressure (P<.001), as well as less lactate dehydrogenase release during reoxygenation (P<.001) and less contraction band necrosis (P<.001) than controls. In the in situ pig heart submitted to 48 minutes of coronary occlusion, the intracoronary infusion of heptanol during the first 15 minutes of reperfusion at a final concentration of 1 mmol/L limited myocardial shrinkage, reflecting hypercontracture (P<.05), reduced infarct size after 5 hours of reperfusion by 54% (P=.04), and modified infarct geometry with a characteristic fragmentation of the area of necrosis. Heptanol at 1 mmol/L had no significant effect on contractility of nonischemic myocardium. CONCLUSIONS: These results demonstrate that hypercontracture may be transmitted to adjacent myocytes through gap junctions and that heptanol may interfere with this transmission and reduce the final extent of myocardial necrosis during reoxygenation or reperfusion. These findings are consistent with the hypothesis tested and open a new approach to limitation of infarct size by pharmacological control of gap junction conductance.

Prevention of ischemic rigor contracture during coronary occlusion by inhibition of Na(+)-H+ exchange.

OBJECTIVE: To determine the effect of Na(+)-H+ exchange blockade on ischemic rigor contracture and reperfusion-induced hypercontracture. METHODS: Thirty-six pigs were submitted to 55 min of coronary occlusion and 5 h reperfusion. Myocardial segment length analysis with ultrasonic microcrystals was used to detect ischemic rigor (reduction in passive segment length change) and hypercontracture (reduction in end-diastolic length). RESULTS: Pretreatment with the new, highly selective Na(+)-H+ exchange inhibitor HOE642 before occlusion reduced ischemic rigor (P < 0.05), attenuated segment shrinkage (P < 0.05) during subsequent reperfusion, dramatically reduced infarct size (P < 0.0001) and attenuated arrhythmias (P < 0.01). Inhibition of Na(+)-H+ exchange only during reperfusion by means of direct intracoronary infusion of HOE642 into the area at risk prevented reperfusion arrhythmias but had no effect on final infarct size, while treatment with intravenous HOE642 immediately before reperfusion had no detectable effects. CONCLUSION: These results indicate that inhibition of Na(+)-H+ exchange during ischemia is necessary to limit myocardial necrosis secondary to transient coronary occlusion, and that this action could by mediated by a protective effect against ischemic contracture. Inhibition of Na(+)-H+ exchange only during reperfusion has a partial and transient beneficial effect, but only when the inhibitor reaches the area at risk before reflow.

The role of Na+-H+ exchange occurring during hypoxia in the genesis of reoxygenation-induced myocardial oedema.

To investigate the role of Na(+)-H+ exchange occurring during hypoxia in the genesis of reoxygenation-induced myocardial oedema, isolated perfused rat hearts were submitted to 40 min of hypoxia and 90 min of reoxygenation. The influence of three factors on myocardial water content was analysed according to a 2 x 2 x 2 factorial design; the hearts were perfused at either pH = 7.4 or pH = 7.0, with either HCO3- buffer or HCO3(-)-free HEPES buffer, and in half of the experiments the hypoxic buffer contained HOE642 6.7 micromol/l. In an additional group, 160 min of normoxia resulted in no lactate dehydrogenase (LDH) release and in a 35.8% increase in myocardial water, independently of pH and of the presence of HCO3- in the buffer. In hearts perfused at pH = 7.4, reoxygenation induced LDH release which was reduced (P<0.05) by HOE642 by 20.1%, by HCO3(-)-free perfusion by 57.5%, and by the combination of both by 91.2%. Reoxygenation also induced severe myocardial oedema (26.3% increase (P<0.05) respect to normoxia). HOE642 reduced (P<0.05) reoxygenation oedema by 15.7%, HCO3(-)-free perfusion by 8.9%, and the combination of both by 24.6%. The effects of HCO3(-)-free perfusion could be mimicked in HCO3(-)-perfused hearts by blocking Na(+)-HCO3- cotransport with 4-4'-dibenzanidostilbene-2,2'-disulphonic acid (DIDS). The beneficial and additive effects of HOE642 and of HCO3(-)-free perfusion on oedema were not a mere consequence of their protective effects against the oxygen paradox, since they were observed in groups perfused at pH= 7.0, a condition which virtually prevented LDH release without preventing oedema (19.0% increase in myocardial water). Thus, reoxygenation-induced myocardial oedema may occur in the absence of necrosis, and is largely determined by Na+ gain during hypoxia via Na(+)-H+ exchange and Na(+)-HCO3- cotransport.

Intimal injury in a transiently occluded coronary artery increases myocardial necrosis. Effect of aspirin.

This study tested the hypothesis that intimal injury in a transiently occluded coronary artery limits myocardial salvage. The effect of intimal injury on reactive hyperaemia was investigated in 17 pigs submitted to a 30-min occlusion of the left anterior descending coronary artery (LAD), not resulting in myocardial infarction. Catheter-induced intimal damage increased local platelet deposition (99mTc) and reduced hyperaemia, but did not modify myocardial platelet or polymorphonuclear leucocyte content (myeloperoxidase activity) after 6 h reperfusion. To investigate the influence of intimal injury on the extent of myocardial necrosis secondary to a more prolonged coronary occlusion, and the role of platelets on this influence, 52 pigs were submitted to a double randomization (2x2 factorial design) to 250 mg i.v. aspirin vs. placebo and to coronary intimal injury vs. no coronary damage before a 48-min occlusion of the LAD and 6 h of reperfusion. After excluding 12 animals with reocclusion, coronary intimal injury was associated with larger infarcts (triphenyltetrazolium reaction) in animals receiving placebo (36.2+/-7.0% of the area at risk in animals with intimal injury vs. 10.8+/-3.9% in animals without coronary injury, P=0.006) but not in those receiving aspirin (20.3+/-6.5 vs. 21.7+/-6.5% of the area at risk in animals with and without intimal injury respectively). These results suggest that coronary intimal injury in the reperfused artery may have adverse effects on myocardial salvage by mechanisms other than reocclusion or embolization of platelet aggregates.

Myocardial segment shrinkage during coronary reperfusion in situ. Relation to hypercontracture and myocardial necrosis.

We have investigated the changes in myocardial segment length induced by reperfusion, and their relation to myocyte hypercontracture and contraction band necrosis. Regional wall function was monitored by ultrasonic gauges in 39 pigs submitted to 48-min occlusion of the left anterior descending coronary artery (LAD) and 6h of reperfusion. Infarct size (triphenyltetrazolium reaction), the extent of contraction band necrosis (quantitative histology) and myocardial water content (desiccation) were measured. Reperfusion induced a marked reduction in end-diastolic length of the LAD segment in all animals, maximal within 15 min after reflow. After 30 min of reperfusion, end-diastolic length of the LAD segment remained below the basal value in 15 animals. The 15 animals that showed shrinkage of the reperfused segment did not differ from the remaining animals in heart rate, aortic pressure, or control segment variables, but had larger infarcts (mean +/- SEM: 32.1 +/- 5.4 vs 12.1 +/- 3.2% of the area at risk, P = 0.003). There was an inverse correlation between end-diastolic length of the LAD segment after 30 min of reperfusion and infarct percentage (r = -0.72) or the extent of contraction band necrosis (r = -0.71). End-diastolic length reduction was more pronounced in larger infarcts despite a more severe myocardial oedema. Neither systolic shortening of the LAD segment nor end-diastolic length or systolic shortening of the control segment, or haemodynamic variables after 30 min of reperfusion correlated to infarct percentage or to the extent of contraction band necrosis. It is concluded that myocardial segment shrinkage during reperfusion reflects myocyte hypercontracture leading to contraction band necrosis.

Dissociation between anti-infarct effect and anti-edema effect of ischemic preconditioning.

This study tested the hypothesis that preconditioning, by reducing catabolite accumulation during ischemia, reduces osmotic swelling and myocardial necrosis during subsequent reperfusion. Farm pigs were randomly allocated to one of three groups of treatment: a control group undergoing a 48-min coronary occlusion (CO) of the middle left anterior descending artery, a preconditioned group (2 cycles of 5-min CO and 5-min reperfusion before the 48-min CO), or an intracoronary perfusion group receiving a substrate-free anoxic buffer perfusion into the area at risk between minutes 5 and 10 of the prolonged CO. Animals were killed after 30 min (n = 23) or 6 h (n = 31) of reperfusion. Compared with the control group, both ischemic preconditioning and washout of ischemic by-products by transient anoxic perfusion reduced myocardial edema after 30 min of reperfusion (P < 0.002) by 35 and 32%, respectively, but only ischemic preconditioning reduced final infarct size (by 55%, P < 0.006). Myocardial lactate content before reperfusion, measured in an additional series of 12 experiments, was reduced by 35% in animals receiving preconditioning or intracoronary perfusion. Thus ischemic preconditioning has a marked protective effect against reperfusion edema, and this effect can be explained by reduced catabolite accumulation during ischemia. However, there is no evidence from this study indicating that reduced catabolite accumulation and limited reperfusion edema explain the important anti-infarct effect of ischemic preconditioning.

Contraction band necrosis at the lateral borders of the area at risk in reperfused infarcts. Observations in a pig model of in situ coronary occlusion.

The aim of this study was to test the hypothesis that increased mechanical stress at the lateral borders of the area at risk may render this area more susceptible to ischaemia/reperfusion injury in the absence of collateral flow. The spatial distribution of myocardial necrosis within the territory of a transiently occluded left anterior descending coronary artery was investigated in 31 porcine hearts submitted to 48 min of coronary occlusion and 6 h of reperfusion. Immediately before excising the heart, the left anterior descending coronary artery was re-occluded and 10% fluorescein was injected in the left atrium. The area at risk was imaged by ultraviolet illumination of the myocardial slices, and the area of necrosis by incubation in triphenyltetrazolium chloride. The area at risk was divided in four sectors and an index of eccentricity was calculated as the percent of the area of necrosis located in the two lateral sectors of the area at risk. The area of contraction band necrosis was measured in whole heart histological sections. Infarcts were generally small, and were composed almost exclusively of contraction band necrosis. There was a good correlation between the extent of the area of contraction band necrosis and infarct size (r = 0.831, P < 0.0005). The area of necrosis had a patchy appearance and was predominantly distributed along the lateral borders of the area at risk. This eccentric distribution was more prominent in smaller infarcts, and the eccentricity index was inversely correlated with infarct size (r = -0.471, P = 0.007), suggesting that contraction band necrosis occurs first at the interface between control and reperfused myocardium in this model. These results are in agreement with a prominent role of mechanical factors in the genesis of myocardial necrosis during transient coronary occlusion.

Analysis of myocardial oedema by magnetic resonance imaging early after coronary artery occlusion with or without reperfusion.

OBJECTIVE: The aim was to analyse the relationship between magnetic resonance (MR) imaging parameters and myocardial water content early after coronary occlusion with or without reperfusion. METHODS: 21 pigs were used. After 78 min of coronary occlusion (n = 7) or 48 min of coronary occlusion and 30 min of reperfusion (n = 14) the heart was excised. In seven animals in the reperfusion protocol the area at risk was perfused for 5 min with an anoxic buffer, starting 5 min after coronary occlusion. Serial T2 weighted and density weighted images of the heart were obtained from apex to base, by using a 1.5 tesla magnetic resonance imager. Water content was measured in samples from control and at-risk myocardium and relaxation parameters were measured in corresponding areas of the magnetic resonance images. RESULTS: Water content was 399(SEM 2) ml x 100 g-1 dry tissue in control myocardium, 427(8) in ischaemic myocardium, and 511(8) in reperfused myocardium (p < 0.001). Reperfused myocardium that had received intracoronary infusion contained less water than myocardium that did not: 498(9) v 534(4) ml x 100 g-1 (p = 0.003). T2 relaxation time and T2 weighted signal intensity in the different sampling sites of magnetic resonance images correlated well with water content in the corresponding myocardial samples (r = 0.76 and r = 0.83) and with the relative volume of extracellular space, as calculated by quantitative histology (r = 0.58 and r = 0.59, p < 0.001). The increase in T2 weighted signal intensity in the area at risk with respect to control myocardium allowed differentiation between ischaemic and reperfused myocardium [9(8)% v 63(3)% respectively]. The area at risk measured by MR imaging correlated very well with that determined at pathology by the fluorescein method (r = 0.92). CONCLUSIONS: Magnetic resonance imaging allows evaluation of myocardial oedema associated with acute coronary occlusion and reperfusion, and analysis of its spatial distribution. Changes in myocardial water content occurring early during acute myocardial infarction allow quantification of the area at risk and detection of reperfusion by magnetic resonance imaging.

Selective inhibition of the contractile apparatus. A new approach to modification of infarct size, infarct composition, and infarct geometry during coronary artery occlusion and reperfusion.

BACKGROUND: Myocardial reperfusion is associated with calcium overload and cell contracture, mechanisms that may precipitate cell death. In this study, we tested the hypothesis that in vivo inhibition of this contracture could lead to cell preservation in an open-chest large animal model. METHODS AND RESULTS: Regional myocardium function was measured during a selective intracoronary infusion of 2,3-butanedione monoxime (BDM), a specific inhibitor of actin-myosin coupling, in the control state (10 pigs) and in a protocol of a 51-minute coronary occlusion followed by reperfusion (40 pigs). The effects on coronary artery blood flow in the basal state were also studied (seven pigs). Intramyocardial distribution of the infusate during coronary occlusion, myocardial water content after 30 minutes of reperfusion and area at risk, infarct size, type of histological necrosis, and infarct geometry after 24 hours of reperfusion were assessed. Methods used included electromagnetic flowmeter, radiolabeled microspheres, subendocardial sonomicrometers, fluorescein, triphenyl tetrazolium chloride and Masson's trichrome staining, and computer quantification of infarct edges. In the absence of ischemia, BDM infusion inhibited regional shortening in a dose-dependent manner up to full systolic bulging while producing marked regional increase in coronary blood flow. During early reperfusion, BDM reduced end-diastolic length 76% more than the control infusion (p less than 0.05) and increased systolic bulging by 420% compared with no change in control animals. The ratio of infarct size/area at risk was reduced by 31% with BDM (p less than 0.05), with striking modifications of infarct histology and infarct geometry; specifically, the extent of contraction band necrosis was reduced by 63% from 105.5 +/- 18.2 to 39.2 +/- 13.6 mm2 (p less than 0.02), and more patches of necrosis (6.5 +/- 2.1 versus 1.6 +/- 0.4, p less than 0.05) and higher contour (7.7 +/- 1.2 versus 5.03 +/- 0.2, p less than 0.05) and fractal (12.1 +/- 1.3 versus 7.8 +/- 0.2, p less than 0.05) indexes were found. CONCLUSIONS: Selective intracoronary infusion of BDM at doses inhibiting regional wall motion decreased infarct size after reperfusion. The effects of BDM on regional function, the reduction in contraction band necrosis at histology, and the peculiar configuration of these infarcts all suggest that inhibition of contracture can interfere with cell-to-cell progression of myocardial necrosis, supporting a role for contracture in reperfusion-induced cell death.

Favorable effects of hyperosmotic reperfusion on myocardial edema and infarct size.

Myocardial water content and infarct size were studied in 39 pigs randomly assigned to a nonintervention group, a group with an intracoronary infusion of a control solution, and a group with a hyperosmotic infusion to 450 mosM by the addition of D-mannitol. The intracoronary solutions were selectively infused into the left anterior descending coronary artery just distal to the occlusion site starting 48 min after occlusion. Reperfusion was performed 3 min later and the infusion rate progressively tapered off over the following 33 min. Multiple myocardial fragments were then obtained in nine pigs, from endocardial, mesocardial, and epicardial regions of the ischemic and control myocardium. Water content measured after 48 h of dessication was significantly greater in the reperfused [530 +/- 7 ml/100 (mean +/- SE) g dry wt] compared with control myocardium (374 +/- 3; P less than 0.0001) and similar in reperfused control and isotonic infusion groups (556 +/- 7 and 543 +/- 8 ml/100 g dry wt); it was 491 +/- 11 with intracoronary D-mannitol infusion, representing 35% less increase (P less than 0.001). In the 30 remaining pigs, area at risk and infarct size were measured 24 h later by in vivo fluorescein and in vitro triphenyltetrazolium chloride. Infarct size was similar in control and in the isotonic reperfused hearts, 6.80 +/- 1.05 and 6.22 +/- 0.76% of ventricular weight, and smaller with D-mannitol, 4.46 +/- 0.46 (P less than 0.05). The ratio of infarct size to area at risk was also smaller [0.415 +/- 0.029 vs. 0.543 +/- 0.052 and 0.547 +/- 0.045 (P less than 0.02)].(ABSTRACT TRUNCATED AT 250 WORDS)

Intracoronary infusion of superoxide dismutase and reperfusion injury in the pig heart.

The effects of an intracoronary infusion of superoxide dismutase on infarct size were studied in 16 pigs submitted to a 48-min coronary occlusion of the mid left anterior descending coronary artery followed by reperfusion for 24 h. Areas at risk marked with fluorescein and infarct sizes calculated with triphenyl tetrazolium chloride staining 24 h after the occlusion were similar in the five control animals with coronary reperfusion alone, in the five animals with an intracoronary infusion of lactate Ringer initiated 3 min before reperfusion and maintained for 33 min and in the six animals with superoxide dismutase added to the solution of lactate Ringer and infused at a rate of 2500 units/min. The ratios infarct size/area at risk were respectively 0.50 +/- 0.10, 0.65 +/- 0.04 in the three study groups (NS). The extent of intramyocardial hemorrhage, evaluated by morphometric analysis was also similar 0.90 +/- 0.29 x 10(6), 0.70 +/- 0.14 and 1.62 +/- 0.42 red blood cells/mm3 of tissue (NS). The superoxide dismutase infusion, however, resulted in significantly fewer early reperfusion arrhythmias which involved 23 +/- 15 s of each minute electrocardiographic recording in the superoxide dismutase group, compared to 37 +/- 13 s in the lactate Ringer group and 45 +/- 14 s in the control group (p = 0.004). The lack of an effect of intracoronary infusion of superoxide dismutase on infarct size suggests that in this experimental model, extracellular superoxide radicals generated during early reperfusion have no major role on myocardial cell necrosis and microvascular damage. Reperfusion arrhythmias were, however, reduced.

Determinants of hemorrhagic infarcts. Histologic observations from experiments involving coronary occlusion, coronary reperfusion, and reocclusion.

Quantification of intramyocardial hemorrhage was performed in 69 pigs submitted to various protocols of coronary artery occlusion and reperfusion. The study groups include 1) permanent occlusion; 2) reperfusion after periods of coronary occlusion of 30, 45, 60, 90, and 120 minutes; 3) reperfusion with diltiazem and with 4) methoxamine after a 60-minute occlusion period; and 5) permanent reocclusion after a 30-minute period of reperfusion. Red blood cell counts were directly assessed by visual examination of histologic slices of myocardium and in a subgroup of animals by counts of red blood cells labeled with 99m-technetium pertechnetate. Hemorrhage occurs in infarcts reperfused after a duration of 45 minutes or more of coronary occlusion and after a period of reperfusion maintained for at least 30 minutes. Red blood cell counts were maximal in the mid portions of transmural sections of the infarcts, with decreasing values toward epicardium and endocardium. Diltiazem decreased total red blood cell counts, whereas methoxamine increased it and also caused subendocardial hemorrhage. The most powerful predictors of the severity of hemorrhage after sustained reperfusion were infarct size and higher blood pressure.

Cell-to-cell interaction: a mechanism to explain wave-front progression of myocardial necrosis.

Histological sections performed 24 h after coronary occlusion in eight pigs displayed compact infarcts extending transmurally with well-defined edges; reconstruction and inspection of the area of necrosis showed a geometric distribution of the infarcts with very irregular, interdigitating edges always in continuity with the main mass of necrosis. Reperfusion in 32 pigs after periods of coronary occlusion of 90, 60, 45, and 30 min exponentially reduced infarct size and transmural extension of the infarct but did not modify its geometry. The two-dimensional size, progression, and geometry of the infarcts could be reproduced by a computer model. In the simulated infarcts, each myocardial cell within the area at risk was represented by a pixel. The algorithm included an inner loop, which determined at random at each iteration a status of reversible or irreversible damage to all pixels. The number of iterations could reproduce infarct of various sizes. With the addition of an index of transmural sensitivity to ischemia, progression of the infarct area could also be reproduced. The only possible means of reproducing the geometry of the infarct was to enter into the program a contiguity condition requiring a direct contact between irreversibly damaged pixels. These observations suggest that the physical interaction between cells is an important determinant of progression of necrosis during coronary occlusion.

Influence of tachycardia and arterial hypertension on infarct size in the pig.

To investigate the clinically important but controversial question of how hypertension during coronary occlusion affects infarct size 24 pigs underwent 1 h occlusion of the mid left anterior descending coronary artery and 24 h reperfusion and were randomised to one of three treatment groups. In group 1 blood pressure was increased during the occlusion period by an infusion of methoxamine; in group 2 tachycardia was induced by atrial pacing; and in group 3 no intervention was performed. The area at risk and infarct size were quantified by digital planimetry of slices of myocardium previously marked with fluorescein and with triphenyl-tetrazolium. Methoxamine maintained mean aortic blood pressure at 117 (SEM8) mmHg during occlusion, whereas the values were 80(6) mmHg in group 2 and 67(9) mmHg in group 3. Pacing increased heart rate to 146(1) beats.min-1 in group 2; it was 103(5) in group 1 and 99(8) in group 3. The pressure-rate product achieved was similar in groups 1 and 2 and significantly higher than in group 3. The pathological studies showed infarct size to be moderately but significantly larger in group 1 (14[3.5]% of the left ventricle) and similar in groups 2 (10.5[3.9]%) and 3 (10.1[2.2]%). The ratio of infarct size to area at risk was also significantly higher (0.743[0.057]) in group 1 with no differences between group 2 (0.604[0.055]) and group 3 (0.613[0.027]). At similar pressure-rate product, infarct size was thus greater with hypertension but not with pacing alone, showing a deleterious effect of increasing blood pressure in this experimental model with negligible collateral blood flow.

Diltiazem and progression of myocardial ischemic damage during coronary artery occlusion and reperfusion in porcine hearts.

This study was designed to investigate whether a cardioprotective intervention could delay the completion of necrosis so that subsequent reperfusion would be more useful. Thirty-six pigs were randomly allocated to treatment with diltiazem (15 micrograms/kg per min) or saline solution and to a 60 or 120 minute coronary occlusion period followed by reperfusion. The treatment was begun 15 minutes before coronary occlusion and terminated 75 minutes after reperfusion. Twenty-four hours after the procedure, the heart was sliced and incubated in triphenyltetrazolium chloride. The infarct area and the maximal transmural area of extension of the infarct were calculated by planimetry. The total number of red blood cells in a transmural section was also counted. In the pigs with a 60 minute coronary occlusion, diltiazem (compared with saline solution) significantly reduced infarct size from 9.7 +/- 1.5% of left ventricular mass to 5.9 +/- 0.6% (p less than 0.05) and the percent transmural extension from 0.72 +/- 0.05 to 0.61 +/- 0.05% (p less than 0.05). Red blood cell extravasation in the infarcted area was reduced from 161,934 +/- 59,905 to 78,525 +/- 46,484 cells/mm3 (p less than 0.05) with diltiazem and the percent transmural extension of the hemorrhagic necrosis from 70 +/- 10 to 36 +/- 15% (p less than 0.05). No such differences were observed in the 120 minute coronary occlusion groups. Mean red blood cell counts and the extent of hemorrhagic necrosis did not correlate with either infarct size or transmural extension.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial reperfusion in the pig heart model: infarct size and duration of coronary occlusion.

The effect of coronary artery reperfusion on infarct size was studied in a pig heart model. Forty four open chest pigs underwent occlusion of the mid-left anterior descending artery. Fifteen minutes after occlusion the animals were randomised to one of five groups: reperfusion at 30, 45, 60, or 90 min after occlusion (groups 1-4) or permanent occlusion (group 5). Twenty four hours after coronary occlusion the pigs were killed. The heart was sectioned in slices, which were incubated in triphenyl-tetrazolium. Mean(SEM) infarct sizes calculated by planimetry were 0.46(0.42), 2.85(1.14), 9.74(1.65), 8.93(1.37), and 13.17(1.17)% of left ventricular mass in the five groups. The transmural extension of the infarct was 14.6(11.4), 42.1(12.9), 87.4(6.6), 96.2(3.2), and 100(0)% and a transmurality index used as an estimate of the mean extension of the infarct relative to wall thickness was calculated to be 0.08(0.06), 0.32(0.10), 0.72(0.06), 0.79(0.04), and 0.92(0.02) respectively. Infarct size was similar in groups 3-5, but significantly smaller in groups 1 and 2 (p less than 0.05). Infarct size and the transmurality index correlated exponentially with the duration of the occlusion (r = 0.80, p less than 0.01; and r = 0.95, p less than 0.001 respectively). These results indicate that in the pig heart model submitted to an acute coronary occlusion cell viability may be less than that suggested by previous canine studies. This observation is probably related to a less well developed collateral blood flow in the pig heart and may provide an experimental model that better resembles certain clinical conditions.