Biomedical subjects

S L Hale

Publications and source records attributed to S L Hale.

At least 19 recordsLinked to original sources

PubMed2000

Location as a determinant of myocardial infarction in rabbits.

Determinants of infarct size in the rabbit heart include risk zone size, regional myocardial blood flow (RMBF), temperature and duration of ischemia. However, other factors might contribute, such as the location of the risk zone (apex to base), independent of known factors. Occlusion of a large marginal branch of the circumflex artery in the rabbit produces a risk region that typically comprises the entire apex of the left ventricle with decreasing area involvement from apex to base. In a retrospective study of 65 rabbit hearts (subjected to 30 min of coronary artery occlusion) which had been sliced into six to eight cross-sectional slices, average area at risk (AR) comprised 86+/-3% of the apical level, 68+/-2% of the middle level and 39+/-2% near the site of occlusion at the base of the heart. If necrosis were dependent on AR alone, then infarct size (area of necrosis/area at risk, AN/AR) would not vary by site. However, AN/AR in the apex was 54+/-3% while AN/AR near the base was 27+/-2%, P<0.0001. To test if this salvage of tissue at risk near the base was due to differences in regional myocardial blood flow, we measured RMBF during occlusion in additional rabbits (n=4). Average RMBF in the risk zone was 0.025 ml/min/g in the apex and 0.010 in the base, P=N.S. Nor was the salvage due to differences in temperature. During occlusion, temperature in the risk zone (n=5) was 38.1 degrees C+/-0.3 in the apex and 38.4+/-0.2 in the base (P=N.S.). When we examined this phenomenon in hearts that received a non-pharmacological intervention that decreases overall infarct size (ischemic preconditioning) and in hearts that received a pharmacological intervention that decreases overall infarct size, a similar pattern of decreasing infarct size as a percentage of the area at risk from apex to base was observed. In conclusion, infarct size as a percentage of the AR depends on whether the AR is at the apex or base of the heart. A larger part of the AR undergoes necrosis toward the apex of the heart. This phenomenon is independent of collateral flow or temperature, and suggests that other as yet unknown factors contribute to infarct size.

Animals↗

PubMed1999

Myocardial hypothermia: a potential therapeutic technique for acute regional myocardial ischemia.

The importance of temperature in the development of necrosis after myocardial ischemia in the beating heart is becoming apparent. Recent studies have shown that the proportion of the ischemic risk zone that becomes necrotic is directly correlated with temperature. This fact suggests the potential therapeutic benefits of reducing myocardial temperature after coronary artery occlusion. We have shown in a number of experimental protocols in the rabbit model of myocardial infarction that topical regional hypothermia reduces infarct size even when instituted after coronary artery occlusion. The reduction in myocardial temperature required to obtain this benefit is modest ( 30 degrees C to 34 degrees C). Topical regional hypothermia allows targeted cooling of a zone of the heart. Myocardial cooling can also be achieved by perfusing the pericardial sac with a chilled fluid by using a closed-circuit catheter system that does not cause cardiac tamponade. This technique also protects myocardium during ischemia. Myocardial hypothermia might be a useful technique to limit ischemic damage during infarction or as adjunctive therapy during minimally invasive cardiac surgery.

Acute Disease↗

PubMed1999

Ischemic preconditioning and myocardial hypothermia in rabbits with prolonged coronary artery occlusion.

This study tests whether combining regional hypothermia and ischemic preconditioning (IP) provides greater myocardial protection during prolonged coronary artery occlusion (CAO) than either intervention alone, and whether increasing the duration of IP from 5 to 7 min extends the window of protection to include a 2-h CAO. Anesthetized rabbits were randomized to four groups (n = 8 rabbits/group): control (C), hypothermia alone (H), IP alone for two 7-min episodes (IP7), and IP plus hypothermia (H + IP7). To compare differences in IP for 5 versus 7 min, additional rabbits (n = 6) received one 5-min episode of ischemia (IP5). All rabbits got 2 h of CAO and 3 h of reperfusion. In comparison with the infarct size in the control group (72 +/- 4% of the risk zone), infarct size was significantly reduced in H (50 +/- 7%), IP7 (49 +/- 5%), and H + IP7 (42 +/- 6%) (all P < 0.05 vs. control group). IP5 failed to confer protection (67 +/- 5% of the risk zone). Therefore, IP can protect against a 2-h CAO if the IP regimen is increased from 5 to 7 min. The combination therapy significantly improved regional myocardial blood flow in the previously ischemic region to a greater extent than either treatment alone.

Animals↗

PubMed1998

Myocardial temperature reduction attenuates necrosis after prolonged ischemia in rabbits.

OBJECTIVE: Previously we observed that a large reduction in infarct size was attained by cooling the risk region of the heart, either before or early after the onset of a 30-min coronary artery occlusion. While this is a standard duration of ischemia used in the rabbit model of infarction, it may not reflect the situation of patients who are reperfused late. The effects of regional hypothermia with a longer duration of ischemia, and when the intervention is applied later, are unknown. This study tests the hypothesis that a local reduction in cardiac temperature protects myocardium during prolonged ischemia (2 h) even if begun well after coronary artery occlusion. METHODS: Anesthetized rabbits received 2 h of coronary artery occlusion and 3 h of reperfusion. Rabbits were randomly assigned to a treated group: topical myocardial cooling starting 30 min after coronary occlusion (n = 14), or control group, no intervention (n = 12). Myocardial temperature in the risk zone, hemodynamics and regional myocardial blood flow were measured. RESULTS: Ischemic zone temperature was similar in both groups at 30 min post occlusion, but the cooling maneuver produced a reduction in temperature in the risk region of the treated group such that myocardial temperature was reduced an average of 10 degrees C between 30 and 60 min of coronary artery occlusion. Myocardial temperature in the control group remained within 0.3 degree C of baseline during coronary artery occlusion and into reperfusion. Core temperatures were similar in both groups. Hemodynamic parameters and collateral blood flow during occlusion were also equivalent in both groups. After 120 min of coronary occlusion, necrosis in the control group comprised 72 +/- 3% of the ischemic risk region. However, in cooled hearts, infarct size, expressed as a fraction of the risk region was significantly lower. Infarct size in this group averaged 59 +/- 3% of the risk region (p < 0.004 vs. controls), and thus cooling resulted in a salvage of approximately 18% of the risk region. CONCLUSION: These results show that reducing myocardial temperature protects ischemic myocardium during a long duration of ischemia even if initiated after coronary artery occlusion.

Analysis of Variance↗

PubMed1998

Hypothermic, closed circuit pericardioperfusion: a potential cardioprotective technique in acute regional ischemia.

OBJECTIVES: This study sought to determine whether infarct size can be reduced by hypothermic pericardioperfusion. BACKGROUND: We have shown that myocardial infarct size can be reduced by topical cooling of the heart. The present study tests whether myocardial cooling and protection can be produced by hypothermic pericardioperfusion using a catheter. METHODS: The catheter was sutured into the pericardial space of anesthetized rabbits. Beginning 30 min before coronary artery occlusion, the space was perfused with either chilled (n = 10) or body temperature (n = 10) fluid. The artery was occluded for 30 min and reperfused for 3 h. RESULTS: After 30 min of pericardioperfusion, myocardial temperature was reduced to 34.1 +/- 0.9 degrees C in chilled hearts compared with 38.9 +/- 0.4 degrees C in control hearts, p < 0.001, a reduction in myocardial temperature of approximately 5 degrees C. Risk areas were similar in both groups (32 +/- 4% left ventricle in cooled and 31 +/- 3% in control hearts, p = NS). However, infarct size in cooled hearts was significantly reduced by 49% (18 +/- 3% of risk area vs. 35 +/- 6%, p = 0.025). Tamponade did not develop, and there were no significant differences in heart rate, arterial pressure or body temperature between groups. CONCLUSIONS: A significant reduction in myocardial temperature, without the development of cardiac tamponade, can be attained using a pericardial catheter to cool the pericardial space. This reduction in temperature causes a significant reduction in necrotic damage. This technique might be used to cool and protect the heart as an adjunct to thrombolysis or during minimally invasive cardiac surgery.

Animals↗

PubMed1997

Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit.

BACKGROUND: Limitation of myocardial infarct size by an earlier brief complete occlusion of a coronary artery is defined as ischemic preconditioning. However, myocardial protection also can be achieved by partial reduction of coronary flow, rapid cardiac pacing, or brief ischemia-reperfusion of a remote region of the heart. Our study assesses the effect on myocardial infarct size of preconditioning at a distance induced by partial reduction of blood flow to a hind limb with or without increase of demand by electrical stimulation of a skeletal muscle. METHODS AND RESULTS: Anesthetized rabbits were randomized to 30 minutes of waiting period (controls), 55% to 65% reduction of femoral artery blood flow (stenosis), electrical stimulation of the gastrocnemius muscle at a rate of one per second (stimulation), or stenosis+stimulation. Thereafter, rabbits underwent 30 minutes of coronary artery occlusion and 4 hours of reperfusion. Each group included 8 rabbits. Risk zones were comparable among groups. However, the ratio of infarct size to risk zone was smaller in the stenosis+stimulation group (0.09+/-0.02) compared with the control (0.26+/-0.03), stenosis (0.36+/-0.05), and stimulation (0.30+/-0.05) groups (P=.0006). ANCOVA performed on the fraction of infarction (infarct size/left ventricular weight) and the fraction of risk zone revealed a significant group effect (P=.0004). CONCLUSIONS: Remote ischemia of a skeletal muscle induced by muscle stimulation combined with restriction of blood flow preconditioned the myocardium. The combination of muscle stimulation with reduction of femoral arterial blood flow but not muscle stimulation without blood flow restriction or of flow restriction without muscle stimulation reduced myocardial infarct size considerably.

Animals↗

PubMed1997

Differences in reperfusion length following 30 minutes of ischemia in the rabbit influence infarct size, as measured by triphenyltetrazolium chloride staining.

Assessment of myocardial infarct size in acute experimental models is usually done by triphenyltetrazolium-chloride (TTC) staining. A certain period of reperfusion is mandatory for discrimination of the infarct zone, especially after relatively short ischemic periods. However, it is unclear what the optimal reperfusion time is for full delineation of the infarct following 30 min of myocardial ischemia in the rabbit. This study compares infarct size, assessed by TTC, in anesthetized open-chest rabbits subjected to 30 min of coronary artery occlusion followed by either 2 (n = 14) v 4 (n = 14) (protocol 1), or 3 (n = 8) v 6 (n = 7) h of reperfusion (protocol 2). Area at risk was assessed by blue dye and necrotic zone by TTC staining. Protocol 1: heart rate and mean blood pressure were comparable in both groups throughout the protocol. Regional myocardial blood flows in both the ischemic and non-ischemic zones during ischemia and after 2 h of reperfusion were comparable between the groups. Regional myocardial blood flow in the post-ischemic zone deteriorated between 2 and 4 h (1.11 +/- 0.15 v 0.58 +/- 0.09 ml/min/g, respectively, P = 0.0004) of reperfusion. The size of the area at risk was comparable (0.31 +/- 0.03 v 0.33 +/- 0.03 of the LV weight in the 2 and 4 h reperfusion groups). However, the ratio of the necrotic zone to the ischemic zone at risk was 63% larger in the 4 compared to the 2 h of reperfusion group (0.31 +/- 0.04 v 0.19 +/- 0.05, respectively, P = 0.02). Analysis of covariance performed on the weight of tissue that developed necrosis and the weight of ischemic zone at risk revealed a significant effect of the reperfusion time (P = 0.014). Protocol 2: there was no difference in infarct size between rabbits subjected to three (0.38 +/- 0.05 of the area at risk) v 6 h (0.41 +/- 0.07) of reperfusion (P = 0.72). Analysis of covariance performed on the weight of tissue that developed necrosis and the weight of ischemic zone at risk did not reveal a significant effect of the reperfusion time. Infarct size as assessed by TTC following 30 min of myocardial ischemia, is smaller when measured 2 h after reperfusion than after 4 h of reperfusion. At least 3 h of reperfusion is needed to delineate infarct size by tetrazolium staining following 30 min of ischemia.

Animals↗

PubMed1997

Regional hypothermia reduces myocardial necrosis even when instituted after the onset of ischemia.

UNLABELLED: Previously, we observed that reducing myocardial temperature in the risk region before coronary artery occlusion caused a profound reduction in infarct size. It is unknown whether lowering myocardial temperature after ischemia has already begun, or just before reperfusion, is also effective in reducing infarct size. This study tests the hypothesis that reducing myocardial temperature locally, after coronary occlusion, reduces infarct size. METHODS: Anesthetized rabbits received 30 min of coronary artery occlusion and three hours of reperfusion. Myocardial temperature in the risk zone was monitored. Rabbits were randomly assigned to one of three groups: group 1, topical myocardial cooling starting 10 min after coronary occlusion (n = 11); group 2, cooling starting 25 min after coronary occlusion (n = 11); or group 3, control, no intervention (n = 10). RESULTS: Hemodynamic parameters and regional myocardial blood flow were equivalent in all groups. Risk zone temperature was similar in all groups at occlusion. The cooling maneuver produced a rapid reduction in temperature in the risk region. In group 1, myocardial temperature was reduced an average of 6.3 degrees C between 10 and 15 min of coronary artery occlusion; myocardial temperature in group 2 was reduced an average of 5.9 degrees C between 25 and 30 min of coronary artery occlusion. Cooling was maintained until 15 min of reperfusion. Myocardial temperature in group 3 remained within 0.3 degree C of baseline during coronary artery occlusion and into reperfusion. Core temperature was similar in all groups. Although the ischemic risk region was comparable in all groups, early cooling (group 1) resulted in a significant reduction in infarct size, expressed as a fraction of the risk region, compared with the control group (0.23 +/- 0.04 vs. 0.44 +/- 0.04 of the risk region); however, cooling just before reperfusion (group 2) failed to modify infarct size compared with the controls (0.43 +/- 0.04 and 0.44 +/- 0.04 of the risk region, respectively). CONCLUSION: These results support our hypothesis that reducing myocardial temperature reduces infarct size. However, it is important the reduction in temperature be produced as early as possible following coronary artery occlusion.

Animals↗

PubMed1997

Is warm retrograde blood cardioplegia better than cold for myocardial protection?

BACKGROUND: This study tests the hypothesis that continuous normothermic retrograde blood cardioplegia is superior to cold intermittent blood cardioplegia in protecting the left and right side of the heart transmurally during an extended cross-clamping period. METHODS: Twelve anesthetized, open chest dogs were placed on cardiopulmonary bypass and randomized to receive continuous warm (n = 6) or intermittent cold cardioprotection (n = 6) during a 3-hour aortic cross-clamp period. Transmural left ventricular muscle biopsy specimens were taken before the initiation of cardiopulmonary bypass and 90 and 180 minutes after cross-clamping. Right ventricular (RV) biopsy specimens were taken 180 minutes after aortic cross-clamping. Biopsy specimens were analyzed for adenosine triphosphate, creatine phosphate, and lactate levels and for morphologic changes via electron microscopy. RESULTS: At the end of 180 minutes of cardiopulmonary bypass, the adenosine triphosphate contents of endocardial and epicardial halves of the left ventricular myocardium were only slightly degraded in both cardioplegia groups; a significantly greater reduction in adenosine triphosphate levels occurred in the RV of the warm compared with the cold group (p < 0.02). The difference in creatine phosphate values in the left ventricle between the cold group (35.2 +/- 23.4 nmol/mg cardiac protein) and the warm animals (64.4 +/- 24.9 nmol/mg cardiac protein) was not statistically significant, but the RV creatine phosphate stores were significantly better preserved in the warm compared with the cold cardioplegia group (p < 0.02). Lactate levels increased to a similar extent in both groups, but both values rose significantly over baseline (p < 0.03). Importantly the electron microscopic score of the left ventricle and RV indicated that cells were reversibly and not irreversibly damaged with both cardioplegic protections. CONCLUSIONS: These results suggest the following: (1) Chemical arrest is a major contributor of myocardial preservation during diastolic arrest as used in clinical cardiac surgery. (2) Both methods preserve the ultrastructure of the myocytes transmurally during 3 hours of aortic cross-clamping. (3) Both techniques protect the RV and left ventricle; however, to provide optimal protection of the RV, alternated retrograde and antegrade perfusion might be beneficial over retrograde cardioplegia flow alone, in particular with warm cardioplegia.

Adenosine Triphosphate↗

PubMed1997

Changes in R wave amplitude: ECG differentiation between episodes of reocclusion and reperfusion associated with ST-segment elevation.

This study assesses the electrocardiographic (ECG) differences between episodes of increased ST-segment amplitude induced by coronary artery occlusion and by reperfusion in the open-chest rabbit model. Nine anesthetized open-chest male New Zealand White rabbits were subjected to four episodes of 5 minutes of coronary artery occlusion followed by 5 minutes of reperfusion. The ST-segment and R wave amplitudes were measured from an ECG lead attached to the pericardium overlying the ischemic myocardium. In 10 out of 35 (29%) of the episodes, reperfusion resulted in a transient increase in ST-segment amplitude. While episodes of coronary artery occlusion were associated with increase in R wave amplitude (69% and 97% of the episodes after 1 and 5 minutes, respectively), all reperfusion episodes were associated with prompt decrease in R wave amplitude. There was no difference between the repeated episodes in the occurrence of ST-segment elevation during reperfusion. However, ST-segment elevation during reperfusion could be distinguished from the ischemic episodes by the prompt decline in the R wave amplitude in the former compared with no change or increase in the latter.

Animals↗

PubMed1997

Myocardial temperature in acute myocardial infarction: protection with mild regional hypothermia.

This study tests the hypothesis that a 2-4 degrees C reduction in myocardial temperature, obtained by using topical regional hypothermia (TRH), reduces infarct size. Anesthetized rabbits received coronary artery occlusion and reperfusion. We cooled hearts in the TRH group by applying an ice bag directly over the risk zone; the control group received no intervention. Risk zone myocardial temperature (MT) in the TRH group was reduced at occlusion by 2 degrees C from baseline and after 5 min of occlusion by 3.6 degrees C. In the control group, MT in the risk region remained within 0.3 degree C of baseline. The ischemic area was similar in both groups, yet infarct size in the TRH group was reduced by an average of 65% compared with the control group. Infarct size closely correlated with MT in the risk region at the time of occlusion. In a second protocol in which all hearts were paced, infarct size was 21% of the risk region in TRH hearts compared with 44% in controls. These results strongly support the important role of MT in the progression of necrosis and demonstrate that the application of local cooling to the risk region profoundly reduces myocardial infarct size.

Animals↗

PubMed1996

Progressive decrease in the ST segment elevation during ischemic preconditioning: is it related to recruitment of collateral vessels?

This study assesses the effect of ischemic preconditioning (IP) on the magnitude of ST segment shift. Anesthetized rabbits were subjected to IP (four periods of 5-min coronary artery occlusion followed by 5-min reperfusion; n = 9) or control (no IP; n = 9). Thereafter, both groups were subjected to 60 min of ischemia. There was a gradual decline in the magnitude of ST segment elevation, recorded by an epicardial lead overlying the ischemic zone. ST amplitude after 1 min of ischemia was 2.19 +/- 0.51, 1.29 +/- 0.44, 0.72 +/- 0.26, 0.20 +/- 0.10, and 0.26 +/- 0.13 mV, during the first, second, third, fourth IP episodes and the final ischemic period respectively (P = 0.0003). ST amplitude after 2 min of ischemia was 2.56 +/- 0.69, 2.47 +/- 0.55, 1.82 +/- 0.42, 1.13 +/- 0.23, and 1.02 +/- 0.14 mV, respectively (P = 0.0043). While heart rate and mean blood pressure at 1, 2, 30, and 60 min of the final long ischemia were similar in both groups, the IP group had less ST elevation (P = 0.0074). There was no change in RMBF between the first IP and the final occlusion. Both groups were equally ischemic during the long occlusion. In the rabbit, progressive reduction in ST segment shift with repeated ischemia is caused by preconditioning and is independent of the recruitment of collaterals or of hemodynamic changes.

Animals↗

PubMed1996

beta-Estradiol, but not alpha-estradiol, reduced myocardial necrosis in rabbits after ischemia and reperfusion.

Recent studies in several animal models have suggested that estrogen, given for the short term, may protect ischemic myocardium. Our objective was to test the effect of exogenous estradiol on the development of myocardial necrosis. Twenty minutes before coronary occlusion, rabbits were given an IV bolus of either 17 beta-estradiol, a form of the hormone that stimulates the estrogen receptor (10 micrograms) or 17 alpha-estradiol, a natural form of the hormone lacking estrogenic effects (1 mg), or vehicle. Regional myocardial blood flow (RMBF) was measured after treatment and during occlusion and reperfusion, and heart rate and blood pressure were monitored throughout. All rabbits underwent 30 minutes of coronary artery occlusion and 4 hours of reperfusion. Estradiol levels were 6 +/- 2 pg/ml in untreated rabbits, 392 +/- 78 pg/ml in rabbits given 17 beta-estradiol, and 413 +/- 68 pg/ml in rabbits given 17 alpha-estradiol. The size of the ischemic region was similar in all groups, but rabbits treated with 17 beta-estradiol developed significantly less necrosis than did control rabbits (0.33 +/- 0.04 vs 0.53 +/- 0.05 of the area at risk; p < 0.05), whereas rabbits treated with 17 alpha-estradiol did not (0.43 +/- 0.03; p = NS vs control group). Heart rate, systemic pressure, and RMBF were comparable among groups throughout the protocol. In conclusion, 17 beta-estradiol exerts a protective effect on ischemic myocardium, reducing infarct size. This beneficial effect is not associated with an increase in myocardial blood flow or alteration in hemodynamics. Because 17 alpha-estradiol did not affect infarct size, the cardioprotective effect of 17 beta-estradiol is probably receptor mediated.

Animals↗

PubMed1996

Direct evidence that ischemic preconditioning does not cause protein kinase C translocation in rabbit heart.

OBJECTIVE: Indirect pharmacological evidence suggests that myocardial protection conferred by ischemic preconditioning in rabbit myocardium is mediated through the translocation of protein kinase C (PKC). To test this hypothesis, we performed direct biochemical measurements of subcellular distribution of PKC in rabbit hearts. METHODS: Two protocols were utilized. In Protocol I the preconditioned group (PC) underwent two 5-min episodes of brief coronary artery occlusion each followed by 5 min of reperfusion, while the control group consisted of time-matched, sham-operated (non-ischemic) animals (SO). Tissue samples were homogenized and cytosolic and particulate fractions were obtained by ultracentrifugation. In Protocol II one group of rabbits received ischemic preconditioning as in Protocol I followed by 10 min of sustained ischemia (PC + IS); a second control group was subjected to 10 min of sustained ischemia (IS); and the third group was time-matched, sham-operated (non-ischemic) animals (SO). Homogenized tissue samples were separated into cytosolic, nuclear and membrane fractions. RESULTS: In Protocol I, no differences in the subcellular distribution of PKC between the SO and PC groups were observed. In Protocol II, when samples were obtained at 10 min of sustained ischemia, no changes in the subcellular distribution of PKC were observed between SO, IS and PC + IS groups. CONCLUSION: Our results indicate that translocation of protein kinase C is not an important mediator of ischemic preconditioning in the rabbit ischemia model.

Animals↗

PubMed1996

The effect of coenzyme Q10 on infarct size in a rabbit model of ischemia/reperfusion.

OBJECTIVE: Coenzyme Q10 has been found to enhance recovery of function after reperfusion in numerous experimental acute ischemia-reperfusion models. We assessed whether coenzyme Q10, administered intravenously either during or 1 h before ischemia, can limit infarct size in the rabbit. METHODS: Anesthetized open-chest rabbits were subjected to 30 min of coronary artery occlusion and 4 h of reperfusion. In Protocol 1, 12 min after beginning of ischemia rabbits were randomized to intravenous infusion of 30 mg coenzyme Q10 (Eisai Co., Japan) (n = 10) or vehicle (n = 10). In Protocol 2, rabbits were randomized to 30 mg coenzyme Q10 (n = 6) or vehicle (n = 6) treatment 60 min before ischemia. Ischemic zone at risk (IZ) was assessed by blue dye and necrotic zone (NZ) by tetrazolium staining. RESULTS: In both protocols, coenzyme Q10 did not alter heart rate, mean blood pressure, or regional myocardial blood flows in either the ischemic or non-ischemic zones during ischemia or reperfusion. No difference was found in IZ (as fraction of LV weight) (Protocol 1: 0.24 +/- 0.02 vs. 0.25 +/- 0.02; Protocol 2: 0.28 +/- 0.02 vs. 0.28 +/- 0.03, in the control vs. coenzyme Q10 groups, respectively). The NZ/IZ ratio was comparable between the groups in both protocols (Protocol 1: 0.22 +/- 0.04 vs. 0.26 +/- 0.04; Protocol 2: 0.21 +/- 0.06 vs. 0.30 +/- 0.06, in the control vs. coenzyme Q10 groups, respectively). CONCLUSIONS: Coenzyme Q10, administered acutely either during or 60 min before myocardial ischemia, does not attenuate infarct size in the rabbit.

Animals↗

PubMed1995

Do antioxidant vitamins reduce infarct size following acute myocardial ischemia/reperfusion?

There is controversy concerning the ability of antioxidant vitamins to reduce myocardial infarct size. We sought to determine whether a brief prophylactic treatment of vitamin C or vitamin C plus Trolox (a water-soluble form of vitamin E) could reduce myocardial infarct size in an experimental model. We used an anesthetized open-chest rabbit model in which a branch of the circumflex coronary artery was ligated for 30 minutes followed by 4 hours of reperfusion. Experiments were performed in a randomized and blinded fashion. An IV injection of normal saline pH balanced to 7.4 (control group n = 15), vitamin C (150 mg/kg, n = 14), or vitamin C plus Trolox (150 mg/kg plus 100 mg/kg, respectively, n = 15) was administered prior to coronary occlusion. Collateral blood flow during coronary occlusion was measured by radioactive microspheres, myocardial risk zone (AR) was assessed by blue dye injection, and myocardial infarct size (AN) was assessed by triphenyltetrazolium chloride staining. All rabbits received comparable ischemic insult: Collateral blood flow and AR were similar among all three groups. Infarct size, measured as a percent of AR, did not differ significantly among the controls (21%), vitamin C (29%), or the vitamin C plus Trolox (18%) groups. Therefore, in this ischemia/reperfusion model, antioxidant vitamins did not alter myocardial infarct size.

Animals↗

PubMed1994

Acute cocaine administration induces ventricular regional wall motion and ultrastructural abnormalities in an anesthetized rabbit model.

Whether acute doses of cocaine can induce left ventricular (LV) regional wall motion abnormalities in animals with otherwise normal coronary arteries is unknown. We studied rabbits receiving constant cocaine infusions (group I: 0.025 to 1.5 mg/kg/min, n = 10), multiple cocaine boluses (group II: 3-5 mg/kg each bolus, n = 10), or saline (group III; n = 8). In group I rabbits, short-axis LV area and diameter increased by 15% to 40% at 60 minutes compared to baseline and to controls (p < 0.01), but percentage of global area fractional shortening was unchanged. Eight rabbits in each of groups I and II, but no controls, developed LV regional wall motion abnormalities as detected by echocardiography: 15 (7 hypokinesis and 8 akinesis or dyskinesis) in the anteroseptal and 2 (hypokinesis) in the posterior LV wall. Among rabbits showing LV wall motion abnormalities, anteroseptal fractional shortening and % area reduction averaged > 20% less (p = 0.03 for area reduction) at 30 minutes versus controls. Only 50% of group I or II rabbits with LV anteroseptal wall motion abnormalities had intraventricular conduction disturbances. Radioactive microsphere flow studies (n = 6) 1 minute after a 4 mg/kg cocaine bolus revealed an equivalent decrease (10% to 20%, average) in septal and LV free wall perfusion (p value not significant). Electron microscopy revealed myocardial cell contraction band necrosis in 3 and sarcoplasmic reticular edema in 7 of 10 cocaine rabbits (unrelated to dose). We conclude that acute cocaine administration in rabbits frequently produces LV anteroseptal wall motion abnormalities even in the absence of differentially decreased perfusion or intraventricular conduction disturbances and produces ultrastructural abnormalities of the myocytes. These findings suggest a direct, nonuniform effect of cocaine on the LV myocardium.

Animals↗

PubMed1994

Protection of myocardium by transient, preischemic administration of phenylephrine in the rabbit.

BACKGROUND: Transient ischemia protects the myocardium from subsequent, more prolonged ischemic episodes; however, other forms of stress before ischemia might also provide a preconditioning effect. Our objective was to test the hypothesis that phenylephrine, an alpha-adrenergic agonist, given before ischemia can act as a pharmacologic preconditioning agent and protect the myocardium. METHODS: Phenylephrine, 50 micrograms/kg, was given as a bolus 15 min before coronary artery occlusion in 11 anesthetized open-chest rabbits; 12 control rabbits received saline. All rabbits underwent 30 min coronary artery occlusion and 4 h reperfusion. Regional myocardial blood flow was quantified using radioactive microspheres, infarct size by tetrazolium staining, and risk zone by blue dye. RESULTS: Pretreatment with phenylephrine significantly reduced necrosis. Infarcted myocardium comprised 23 +/- 4% of the region at risk in treated rabbits compared with 39 +/- 4% in control animals (P < 0.01). Mean systolic arterial pressure increased briefly after administration of phenylephrine (98 +/- 5 to 141 +/- 7 mmHg) but returned to baseline before occlusion. Heart rate was similar in both groups at baseline but decreased slightly with phenylephrine treatment. Regional myocardial blood flow increased after injection of the phenylephrine bolus to 2.86 +/- 0.22 compared with 2.25 +/- 0.08 ml/min/g in control animals (P = 0.02), but both groups were equally ischemic during occlusion. CONCLUSION: Transient, preischemic treatment with phenylephrine makes the myocardium more resistant to necrosis during ensuing ischemia and reperfusion.

Animals↗