Increased myocardial infarct size because of reduced coronary collateral blood flow in beagles

1989 ◽  
Vol 257 (6) ◽  
pp. H1798-H1803 ◽  
Author(s):  
N. Uemura ◽  
D. R. Knight ◽  
Y. T. Shen ◽  
J. Nejima ◽  
M. V. Cohen ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Myocardial Blood Flow ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Circumflex Coronary Artery ◽  
Area At Risk ◽  
Left Circumflex Coronary Artery

Effects of permanent left circumflex coronary artery occlusion (CAO) were examined in conscious purebred beagles and mongrel dogs, instrumented with miniature left ventricular (LV) pressure gauges, wall thickness gauges in the ischemic zone, catheters in left atrium and aorta, and snares around the left circumflex coronary artery. Blood flow was measured using the radioactive microsphere technique before CAO and at 5 min, 1, 3, and 24 h after CAO. Although CAO reduced myocardial blood flow similarly in beagles and mongrels, significantly less (P less than 0.05) recovery of myocardial blood flow was observed over the following 24-h period in beagles. Infarct size, as determined by triphenyltetrazolium chloride and expressed as percentage of area at risk, was larger (P less than 0.05) in beagles (62.0 +/- 5.1%) than mongrels (42.5 +/- 4.2%). Thus beagles do not tolerate ischemia as well as mongrel dogs and possess fewer functional coronary collaterals resulting in larger infarcts after CAO.

An adenosine agonist and preconditioning shift the distribution of myocardial blood flow in conscious pigs

1999 ◽  
Vol 276 (2) ◽  
pp. H368-H375 ◽  
Author(s):  
Cheng-Hsiung Huang ◽  
Song-Jung Kim ◽  
Bijan Ghaleh ◽  
Raymond K. Kudej ◽  
You-Tang Shen ◽  
...  
Keyword(s):  
Blood Flow ◽  
Spatial Distribution ◽  
Coronary Artery ◽  
Myocardial Blood Flow ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Coronary Artery Occlusion ◽  
Myocardial Infarct Size ◽  
Area At Risk ◽  
Cardioprotective Effects

The goal of this study was to determine whether the cardioprotective effects of an A1-receptor agonist and ischemic preconditioning (IPC) involve a shift in the pre-coronary artery occlusion (CAO) spatial distribution of myocardial blood flow, which might shed light on the mechanism of IPC and explain its heterogeneous effects. Accordingly, 60 min of CAO followed by 72 h of coronary artery reperfusion (CAR) was examined in three groups of conscious pigs 10–14 days after instrumentation with aortic and left atrial catheters and coronary artery occluders. Myocardial infarct size, expressed as a fraction of the area at risk (AAR), was reduced significantly ( P < 0.05) by infusion of the A1 agonist (27.1 ± 6.6%) and to a greater extent ( P < 0.05) by IPC (11.6 ± 5.1%) compared with infarct size in vehicle-treated animals (55.1 ± 2.9%). Transmural myocardial blood flow (radioactive microspheres) in the AAR shifted toward lower levels after infusion of the A1 agonist (1.27 ± 0.19 vs. 0.74 ± 0.10 ml ⋅ min−1 ⋅ g−1) or IPC (1.27 ± 0.11 vs. 0.96 ± 0.09 ml ⋅ min−1 ⋅ g−1) but not after infusion of the vehicle (1.20 ± 0.10 vs. 1.23 ± 0.09 ml ⋅ min−1 ⋅ g−1). This study demonstrated that both pretreatment with an adenosine A1 agonist and also IPC altered the spatial distribution of pre-CAO myocardial blood flow, which might reflect a downregulation of metabolic state and thus play a role in the cardioprotective effects of IPC.

Reduction of Myocardial Necrosis after Glycosaminoglycan Administration: Effects of a Single Intravenous Administration of Heparin or N-Acetylheparin 2 Hours before Regional Ischemia and Reperfusion

1996 ◽  
Vol 1 (3) ◽  
pp. 219-228 ◽  
Author(s):  
Michael R. Gralinski ◽  
Edward M. Driscoll ◽  
Gregory S. Friedrichs ◽  
Michael R. DeNardis ◽  
Benedict R. Lucchesi
Keyword(s):  
Infarct Size ◽  
Regional Blood Flow ◽  
Myocardial Infarct ◽  
Myocardial Necrosis ◽  
Final Analysis ◽  
Study Groups ◽  
Left Ventricular ◽  
Coagulation System ◽  
Myocardial Infarct Size ◽  
Area At Risk

Background We determined if a single administration of heparin or nonanticoagulant N-acetylheparin could reduce myocardial injury resulting from a 90-minute occlusion of the left circumflex coronary artery (LCX) and 6 hours of reperfusion in the anesthetized canine. Methods and Results Heparin (2 mg/kg), N-acetylheparin (2 mg/kg), or vehicle, 0.9% sodium chloride (control), was administered intravenously to separate groups of animals 2 hours before LCX occlusion. To ensure parity of LCX ischemia, only animals with ischemic zone regional blood flow < 0.16 mL/min/g tissue were included in the final analysis. Hemodynamics did not differ among the three study groups. Infarct size as a percentage of the left ventricular area at risk was obtained for each group. Myocardial infarct size was 43.0 ± 3.9% in the vehicle, 28.8 ± 5.8% in the heparin ( P < .05 vs vehicle) and 24.7 ± 4.6% ( P < .05 vs vehicle) in the N-acetylheparin-treated animals. Conclusion Pretreatment with heparin or its nonanticoagulant derivative, N-acetylheparin, provides significant protection to the regionally ischemic and reperfused canine myocardium independent of either plasma glycosaminoglycan concentration or alterations in the coagulation system.

Effect of hyperoxia on regional blood flow after coronary occlusion in awake dogs

1980 ◽  
Vol 238 (2) ◽  
pp. H244-H248 ◽  
Author(s):  
F. Rivas ◽  
J. C. Rembert ◽  
R. J. Bache ◽  
F. R. Cobb ◽  
J. C. Greenfield
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Myocardial Blood Flow ◽  
Regional Blood Flow ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Regional Myocardial Blood Flow ◽  
Circumflex Coronary Artery ◽  
Left Circumflex Coronary Artery ◽  
Oxygen Inhalation

The effect of 100% oxygen inhalation on regional transmural myocardial blood flow following 45 s of actue total left circumflex coronary artery occlusion was studied in six awake dogs chronically instrumented with a coronary occluder and catheters in the aorta and left atrium. After inhalation of either room air or 100% oxygen for at least 30 min and following the 45-s occlusion, transmural myocardial blood flow was determined with radioactive microspheres (7--10 micrometers). Each dog underwent two occlusions of the left circumflex coronary artery; one during inhalation of rrom air and the other during 100% oxygen. During room air inhalation, mean regional myocardial blood flow to nonischemic, intermediate, and ischemic regions was 0.92 +/- 0.05, 0.51 +/- 0.08, and 0.10 +/- 0.02 ml . min-1 . g-1, respectively. During 100% oxygen administration, flow was significantly diminished in each region to 0.75 +/- 0.04, 0.41 +/- 0.07, and 0.06 +/- 0.01 ml . min-1 . g-1, respectively. Transmural blood flow to each layer was uniformly reduced in all regions. These data indicate that 100% oxygen further reduces myocardial blood flow to ischemic regions.

Inhibition of adenosine-mediated coronary vasodilation exacerbates myocardial ischemia during exercise

1993 ◽  
Vol 265 (5) ◽  
pp. H1471-H1477 ◽  
Author(s):  
D. D. Laxson ◽  
D. C. Homans ◽  
R. J. Bache
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Myocardial Ischemia ◽  
Myocardial Blood Flow ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Coronary Vasodilation ◽  
Circumflex Coronary Artery ◽  
Left Circumflex Coronary Artery ◽  
Transmural Flow

Persisting coronary vasoconstrictor tone that is responsive to exogenous adenosine administration has been demonstrated during myocardial ischemia. Therefore, the role and extent of endogenous adenosine-mediated coronary vasodilation in opposing coronary vasoconstriction within regions of ischemic myocardium was investigated in 10 chronically instrumented exercising dogs. Studies were performed on dogs with left circumflex coronary artery stenosis during treadmill exercise (6.5 km/h, 6% grade), while myocardial blood flow was measured with radioactive microspheres. Blood flow was measured before and again after inhibition of the effects of endogenously produced adenosine through combined inactivation of adenosine and adenosine receptor antagonism by the administration of intracoronary adenosine deaminase (ADA) (5 micrograms.kg-1 x min-1 x 10 min) plus 8-phenyltheophylline (8-PT) (5 mg/kg i.v.), respectively. Coronary perfusion pressure was held equal during both conditions at approximately 41 mmHg with a hydraulic occluder. During exercise in the presence of a coronary stenosis, blood flow was reduced in all layers of myocardium in regions supplied by the stenosed left circumflex coronary artery compared with blood flow in regions of myocardium supplied by the nonstenotic left anterior descending coronary artery. After ADA plus 8-PT, myocardial blood flow (in ml.min-1 x g-1) was further reduced in all layers of myocardium in regions supplied by the stenotic left circumflex coronary artery compared with baseline (subendocardial layer 0.44 +/- 0.09 vs. 0.67 +/- 0.13 ml.min-1 x g-1, mean transmural flow 0.92 +/- 0.13 vs. 1.25 +/- 0.2 ml.min-1 x g-1, both P < 0.05). Blood flow in regions of myocardium supplied by the nonstenotic left anterior descending coronary artery were unchanged following ADA plus 8-PT.(ABSTRACT TRUNCATED AT 250 WORDS)

Isoflurane-induced preconditioning is attenuated by diabetes

2002 ◽  
Vol 282 (6) ◽  
pp. H2018-H2023 ◽  
Author(s):  
Katsuya Tanaka ◽  
Franz Kehl ◽  
Weidong Gu ◽  
John G. Krolikowski ◽  
Paul S. Pagel ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Protective Effects ◽  
Area At Risk ◽  
End Tidal

Volatile anesthetics stimulate, but hyperglycemia attenuates, the activity of mitochondrial ATP-regulated K+ channels. We tested the hypothesis that diabetes mellitus interferes with isoflurane-induced preconditioning. Acutely instrumented, barbiturate-anesthetized dogs were randomly assigned to receive 0, 0.32, or 0.64% end-tidal concentrations of isoflurane in the absence or presence of diabetes (3 wk after administration of alloxan and streptozotocin) in six experimental groups. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size (triphenyltetrazolium staining) was 29 ± 3% ( n = 8) of the left ventricular area at risk in control experiments. Isoflurane reduced infarct size (15 ± 2 and 13 ± 1% during 0.32 and 0.64% concentrations; n = 8 and 7 dogs, respectively). Diabetes alone did not alter infarct size (30 ± 3%; n = 8) but blocked the protective effects of 0.32% (27 ± 2%; n = 7) and not 0.64% isoflurane (18 ± 3%; n = 7). Infarct size was directly related to blood glucose concentrations in diabetic dogs, but this relationship was abolished by higher concentrations of isoflurane. The results indicate that blood glucose and end-tidal isoflurane concentrations are important determinants of infarct size during anesthetic-induced preconditioning.

scholarly journals Evidence for a role of opioids in epoxyeicosatrienoic acid-induced cardioprotection in rat hearts

2010 ◽  
Vol 298 (6) ◽  
pp. H2201-H2207 ◽  
Author(s):  
Garrett J. Gross ◽  
John E. Baker ◽  
Anna Hsu ◽  
Hsiang-en Wu ◽  
John R. Falck ◽  
...  
Keyword(s):  
Infarct Size ◽  
Pertussis Toxin ◽  
Isolated Heart ◽  
Myocardial Infarct ◽  
Antinociceptive Effect ◽  
Left Ventricular ◽  
Endogenous Opioids ◽  
Myocardial Infarct Size ◽  
Protective Effects ◽  
Area At Risk

We previously demonstrated that several epoxyeicosatrienoic acids (EETs) produce reductions in myocardial infarct size in rats and dogs. Since a recent study demonstrated the release of opioids in mediating the antinociceptive effect of 14,15-EET, we hypothesized that endogenous opioids may also be involved in mediating the cardioprotective effect of the EETs. To test this hypothesis, we used an in vivo rat model of infarction and a rat Langendorff model. In the infarct model, hearts were subjected to 30 min occlusion of the left coronary artery and 2 h reperfusion. Animals were treated with 11,12-EET or 14,15-EET (2.5 mg/kg) alone 15 min before occlusion or with opioid antagonists [naloxone, naltrindole, nor-binaltorphimine (nor-BNI), and d-Phe-Cys-Tyr-d-Trp-Om-Thr-Pen-Thr-NH2 (CTOP), a nonselective, a selective δ, a selective κ, and a selective μ receptor antagonist, respectively] 10 min before EET administration. In four separate groups, antiserum to Met- and Leu-enkephalin and dynorphin-A-(1–17) was administered 50 min before the 11,12-EET administration. Infarct size expressed as a percent of the area at risk (IS/AAR) was 63.5 ± 1.2, 45.3 ± 1.0, and 40.9 ± 1.2% for control, 11,12-EET, and 14,15-EET, respectively. The protective effects of 11,12-EET were abolished by pretreatment with either naloxone (60.5 ± 1.8%), naltrindole (60.8 ± 1.0%), nor-BNI (62.3 ± 2.8%), or Met-enkephalin antiserum (63.2 ± 1.7%) but not CTOP (42.0 ± 3.0%). In isolated heart experiments, 11,12-EET was administered to the perfusate 15 min before 20 min global ischemia followed by 45 min reperfusion in control hearts or in those pretreated with pertussis toxin (48 h). 11,12-EET increased the recovery of left ventricular developed pressure from 33 ± 1 to 45 ± 6% ( P < 0.05) and reduced IS/AAR from 37 ± 4 to 20 ± 3% ( P < 0.05). Both pertussis toxin and naloxone abolished these beneficial effects of 11,12-EET. Taken together, these results suggest that the major cardioprotective effects of the EETs depend on activation of a Gi/o protein-coupled δ- and/or κ-opioid receptor.

Sarcolemmal and Mitochondrial Adenosine Triphosphate– dependent Potassium Channels

2000 ◽  
Vol 92 (6) ◽  
pp. 1731-1739 ◽  
Author(s):  
Wolfgang G. Toller ◽  
Eric R. Gross ◽  
Judy R. Kersten ◽  
Paul S. Pagel ◽  
Garrett J. Gross ◽  
...  
Keyword(s):  
At Risk ◽  
Infarct Size ◽  
Adenosine Triphosphate ◽  
Katp Channel ◽  
Myocardial Infarct ◽  
Katp Channels ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Area At Risk ◽  
Mitochondrial Katp Channels

Background Volatile anesthetic-induced preconditioning is mediated by adenosine triphosphate-dependent potassium (KATP) channels; however, the subcellular location of these channels is unknown. The authors tested the hypothesis that desflurane reduces experimental myocardial infarct size by activation of specific sarcolemmal and mitochondrial KATP channels. Methods Barbiturate-anesthetized dogs (n = 88) were acutely instrumented for measurement of aortic and left ventricular pressures. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3-h reperfusion. In four separate groups, dogs received vehicle (0.9% saline) or the nonselective KATP channel antagonist glyburide (0.1 mg/kg intravenously) in the presence or absence of 1 minimum alveolar concentration desflurane. In four additional groups, dogs received 45-min intracoronary infusions of the selective sarcolemmal (HMR 1098; 1 microg. kg-1. min-1) or mitochondrial (5-hydroxydecanoate [5-HD]; 150 microg. kg-1. min-1) KATP channel antagonists in the presence or absence of desflurane. Myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively. Results Desflurane significantly (P &lt; 0.05) decreased infarct size to 10 +/- 2% (mean +/- SEM) of the area at risk as compared with control experiments (25 +/- 3% of area at risk). This beneficial effect of desflurane was abolished by glyburide (25 +/- 2% of area at risk). Glyburide (24 +/- 2%), HMR 1098 (21 +/- 4%), and 5-HD (24 +/- 2% of area at risk) alone had no effects on myocardial infarct size. HMR 1098 and 5-HD abolished the protective effects of desflurane (19 +/- 3% and 22 +/- 2% of area at risk, respectively). Conclusion Desflurane reduces myocardial infarct size in vivo, and the results further suggest that both sarcolemmal and mitochondrial KATP channels could be involved.

Isoflurane Preconditions Myocardium Against Infarction via  Activation of Inhibitory Guanine Nucleotide Binding Proteins

2000 ◽  
Vol 92 (5) ◽  
pp. 1400-1407 ◽  
Author(s):  
Wolfgang G. Toller ◽  
Judy R. Kersten ◽  
Eric R. Gross ◽  
Paul S. Pagel ◽  
David C. Warltier
Keyword(s):  
Infarct Size ◽  
Pertussis Toxin ◽  
Myocardial Infarct ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Area At Risk ◽  
Rate Of Increase ◽  
Gi Protein

Background Isoflurane-induced myocardial protection during ischemia is mediated by adenosine triphosphate-regulated potassium (KATP) channels; however, the intracellular signal transduction cascade responsible for this process has been incompletely evaluated. The authors tested the hypothesis that isoflurane reduces myocardial infarct size through a Gi protein-mediated process. Methods Forty-eight hours after pretreatment with vehicle (0.9% saline) or the Gi protein inhibitor pertussis toxin (10 microg/kg intravenously), barbiturate-anesthetized dogs (n = 43) were instrumented for measurement of aortic and left ventricular pressures and maximum rate of increase of left ventricular pressure. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3-h reperfusion. In four separate groups, vehicle- or pertussis toxin-pretreated dogs were studied with or without administration of 1 minimum alveolar concentration isoflurane. In two additional groups, dogs received the direct KATP channel agonist nicorandil (100 microg/kg bolus and 10 microg x kg-1 x min-1 intravenous infusion) in the presence or absence of pertussis toxin pretreatment. Myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively. Results Isoflurane significantly (P &lt; 0.05) decreased infarct size to 7 +/- 2% of the area at risk compared with control experiments (26 +/- 2%). Pertussis toxin pretreatment alone had no effects on myocardial infarct size (31 +/- 4%) but blocked the beneficial effects of isoflurane (21 +/- 3%). Nicorandil decreased infarct size (11 +/- 2%), but, in contrast to isoflurane, this effect was independent of pertussis toxin pretreatment (11 +/- 1%). Conclusion Isoflurane reduces myocardial infarct size by a Gi protein-mediated mechanism in vivo.

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