scholarly journals Acetaminophen and myocardial infarction in dogs

2004 ◽  
Vol 287 (5) ◽  
pp. H1913-H1920 ◽  
Author(s):  
Gary F. Merrill ◽  
Tyler H. Rork ◽  
Norell M. Spiler ◽  
Roseli Golfetti
Keyword(s):  
Myocardial Infarction ◽  
Heart Rate ◽  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Infarct Size ◽  
Blood Gases ◽  
Left Ventricular ◽  
Collateral Flow ◽  
Area At Risk ◽  
Developed Pressure

The hypothesis that acetaminophen can reduce necrosis during myocardial infarction was tested in male dogs. Two groups were studied: vehicle- ( n = 10) and acetaminophen-treated ( n = 10) dogs. All dogs were obtained from the same vendor, and there were no significant differences in their ages (18 ± 2 mo), weights (24 ± 1 kg), or housing conditions. Selected physiological data, e.g., coronary blood flow, nonspecific collateral flow, epicardial temperature, heart rate, systemic mean arterial pressure, left ventricular developed pressure, the maximal first derivative of left ventricular developed pressure, blood gases, and pH, were collected at baseline and during regional myocardial ischemia and reperfusion. There were no significant differences in coronary blood flow, nonspecific collateral flow, epicardial temperature, heart rate, systemic mean arterial pressure, or blood gases and pH between the two groups at any of the three time intervals, even though there was a trend toward improved function in the presence of acetaminophen. Infarct size, the main objective of the investigation, was markedly and significantly reduced by acetaminophen. For example, when expressed as a percentage of ventricular wet weight, infarct size was 8 ± 1 versus 3 ± 1%( P < 0.05) in vehicle- and acetaminophen-treated hearts, respectively. When infarct size was expressed as percentage of the area at risk, it was 35 ± 3 versus 13 ± 2% ( P < 0.05) in vehicle- and acetaminophen-treated groups, respectively. When area at risk was expressed as percentage of total ventricular mass, there were no differences in the two groups. Results reveal that the recently reported cardioprotective properties of acetaminophen in vitro can now be extended to the in vivo arena. They suggest that it is necessary to add acetaminophen to the growing list of pharmaceuticals that possess cardioprotective efficacy in mammals.

Is Isoflurane-induced Preconditioning Dose Related?

2002 ◽  
Vol 96 (3) ◽  
pp. 675-680 ◽  
Author(s):  
Franz Kehl ◽  
John G. Krolikowski ◽  
Boris Mraovic ◽  
Paul S. Pagel ◽  
David C. Warltier ◽  
...  
Keyword(s):  
Blood Flow ◽  
Infarct Size ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Collateral Blood Flow ◽  
Area At Risk ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Coronary Collateral Blood Flow

Background Volatile anesthetics precondition against myocardial infarction, but it is unknown whether this beneficial action is threshold- or dose-dependent. The authors tested the hypothesis that isoflurane decreases myocardial infarct size in a dose-dependent fashion in vivo. Methods Barbiturate-anesthetized dogs (n = 40) were instrumented for measurement of systemic hemodynamics including aortic and left ventricular pressures and rate of increase of left ventricular pressure. Dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion and were randomly assigned to receive either 0.0, 0.25, 0.5, 1.0, or 1.25 minimum alveolar concentration (MAC) isoflurane in separate groups. Isoflurane was administered for 30 min and discontinued 30 min before left anterior descending coronary artery occlusion. Results Infarct size (triphenyltetrazolium staining) was 29 +/- 2% of the area at risk in control experiments (0.0 MAC). Isoflurane produced significant (P &lt; 0.05) reductions of infarct size (17 +/- 3, 13 +/- 1, 14 +/- 2, and 11 +/- 1% of the area at risk during 0.25, 0.5, 1.0, and 1.25 MAC, respectively). Infarct size was inversely related to coronary collateral blood flow (radioactive microspheres) in control experiments and during low (0.25 or 0.5 MAC) but not higher concentrations of isoflurane. Isoflurane shifted the linear regression relation between infarct size and collateral perfusion downward (indicating cardioprotection) in a dose-dependent fashion. Conclusions Concentrations of isoflurane as low as 0.25 MAC are sufficient to precondition myocardium against infarction. High concentrations of isoflurane may have greater efficacy to protect myocardium during conditions of low coronary collateral blood flow.

Augmented catecholamine uptake by the heart during hemorrhage in the conscious dog

1986 ◽  
Vol 250 (1) ◽  
pp. H76-H81 ◽  
Author(s):  
O. L. Woodman ◽  
J. Amano ◽  
T. H. Hintze ◽  
S. F. Vatner
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Coronary Blood Flow ◽  
Coronary Sinus ◽  
Nerve Stimulation ◽  
Left Ventricular ◽  
Sympathetic Nerve Stimulation ◽  
Net Release

Changes in arterial and coronary sinus concentrations of norepinephrine (NE) and epinephrine (E) in response to hemorrhage were examined in conscious dogs. Hemorrhage (45 +/- 3.2 ml/kg) decreased mean arterial pressure by 47 +/- 6%, left ventricular (LV) dP/dt by 38 +/- 6%, and mean left circumflex coronary blood flow by 47 +/- 6%, while heart rate increased by 44 +/- 13%. Increases in concentrations of arterial NE (5,050 +/- 1,080 from 190 +/- 20 pg/ml) and E (12,700 +/- 3,280 from 110 +/- 20 pg/ml) were far greater than increases in coronary sinus NE (1,700 +/- 780 from 270 +/- 50 pg/ml) and E (4,300 +/- 2,590 from 90 +/- 10 pg/ml). Net release of NE from the heart at rest was converted to a fractional extraction of 66 +/- 9% after hemorrhage. Fractional extraction of E increased from 16 +/- 6% at rest to 73 +/- 8% after hemorrhage. In cardiac-denervated dogs, hemorrhage (46 +/- 2.8 ml/kg) decreased mean arterial pressure by 39 +/- 15%, LV dP/dt by 36 +/- 10%, and mean left circumflex coronary blood flow by 36 +/- 13%, while heart rate increased by 24 +/- 10%. Hemorrhage increased arterial NE (1,740 +/- 150 from 210 +/- 30 pg/ml) and E (3,050 +/- 880 from 140 +/- 20 pg/ml) more than it increased coronary sinus NE (460 +/- 50 from 150 +/- 30 pg/ml) and E (660 +/- 160 from 90 +/- 20 pg/ml) but significantly less (P less than 0.05) than observed in intact dogs. These experiments indicate that hemorrhage, unlike exercise and sympathetic nerve stimulation, does not induce net overflow of NE from the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in the myocardial area at risk, infarct size, and collateral flow following nicardipine infusion in dogs

1991 ◽  
Vol 69 (12) ◽  
pp. 1789-1796
Author(s):  
Reena Sandhu ◽  
George P. Biro
Keyword(s):  
At Risk ◽  
Blood Flow ◽  
Infarct Size ◽  
Blue Dye ◽  
Collateral Flow ◽  
Collateral Blood Flow ◽  
Area At Risk ◽  
Arterial Blood ◽  
Myocardial Area ◽  
Size Limitation

The area at risk of infarction after an acute occlusion of the left anterior descending coronary artery was defined in anesthetized dogs using the distribution of 99mTc-labelled albumin microaggregates and Monastral blue dye. In thirteen dogs, it was determined that these two particulate labels identified identical areas of unperfused myocardium. In a second group of dogs (n = 12), the risk areas determined at 10 (99mTc-labelled macroaggregates) and at 180 min (Monastral blue dye) were found to be identical, with no change in collateral blood flow, indicating the absence of a spontaneous change in underperfused myocardium over this time. In a third group of dogs (n = 17) nicardipine was infused (10 μg∙kg−1∙min−1 for 5 min, followed by 8 μg∙kg−1∙min−1 for 165 min). This resulted in a significant and sustained fall (32 ± 4 mmHg; 1 mmHg = 133.32 Pa) in mean arterial blood pressure but no significant change in collateral blood flow was found, except for a marginal increase in the center of the ischemic zone. Area at risk and infarct sizes were also not significantly different between the latter two groups (18.2 ± 4.1 vs. 21.6 ± 4.0% of left ventricle). In this model, the magnitude of the area at risk appears to be determined early after a coronary occlusion and appears to be unmodified by treatment with nicardipine begun after the occlusion.Key words: area at risk, nicardipine, collateral flow, risk region, risk zone, infarct size limitation.

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.

scholarly journals Isoflurane Protects against Myocardial Infarction during Early Reperfusion by Activation of Phosphatidylinositol-3-Kinase Signal Transduction: Evidence for Anesthetic-induced Postconditioning in Rabbits

2005 ◽  
Vol 102 (1) ◽  
pp. 102-109 ◽  
Author(s):  
Pascal C. Chiari ◽  
Martin W. Bienengraeber ◽  
Paul S. Pagel ◽  
John G. Krolikowski ◽  
Judy R. Kersten ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
Coronary Occlusion ◽  
Minimum Alveolar Concentration ◽  
Left Ventricular ◽  
Saline Control ◽  
Phosphatidylinositol 3 Kinase ◽  
Area At Risk ◽  
Early Reperfusion ◽  
Phosphatidylinositol 3

Background Brief episodes of ischemia during early reperfusion after coronary occlusion reduce the extent of myocardial infarction. Phosphatidylinositol-3-kinase (PI3K) signaling has been implicated in this "postconditioning" phenomenon. The authors tested the hypothesis that isoflurane produces cardioprotection during early reperfusion after myocardial ischemia by a PI3K-dependent mechanism. Methods Pentobarbital-anesthetized rabbits (n = 80) subjected to a 30-min coronary occlusion followed by 3 h reperfusion were assigned to receive saline (control), three cycles of postconditioning ischemia (10 or 20 s each), isoflurane (0.5 or 1.0 minimum alveolar concentration), or the PI3K inhibitor wortmannin (0.6 mg/kg, intravenously) or its vehicle dimethyl sulfoxide. Additional groups of rabbits were exposed to combined postconditioning ischemia (10 s) and 0.5 minimum alveolar concentration isoflurane in the presence and absence of wortmannin. Phosphorylation of Akt, a downstream target of PI3K, was assessed by Western blotting. Results Postconditioning ischemia for 20 s, but not 10 s, reduced infarct size (P &lt; 0.05) (triphenyltetrazolium staining; 20 +/- 3% and 34 +/- 3% of the left ventricular area at risk, respectively) as compared with control (41 +/- 2%). Exposure to 1.0, but not 0.5, minimum alveolar concentration isoflurane decreased infarct size (21 +/- 2% and 43 +/- 3%, respectively). Wortmannin abolished the protective effects of postconditioning (20 s) and 1.0 minimum alveolar concentration isoflurane. Combined postconditioning (10 s) and 0.5 minimum alveolar concentration isoflurane markedly reduced infarct size (17 +/- 5%). This action was also abolished by wortmannin (44 +/- 2%). Isoflurane (1.0 minimum alveolar concentration) increased Akt phosphorylation after ischemia (32 +/- 6%), and this action was blocked by wortmannin. Conclusions Isoflurane acts during early reperfusion after prolonged ischemia to salvage myocardium from infarction and reduces the threshold of ischemic postconditioning by activating PI3K.

scholarly journals Left ventricular blood flow energetics after acute ST-segment elevation myocardial infarction associate with left ventricular remodeling

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Demirkiran ◽  
P Garg ◽  
R J Geest ◽  
H J Berkhof ◽  
R Nijveldt ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Blood Flow ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Infarct Size ◽  
Logistic Regression Analysis ◽  
Left Ventricular ◽  
St Segment Elevation ◽  
St Segment ◽  
Lv Remodeling

Abstract Background Myocardial infarction (MI) leads to complex changes in left ventricular (LV) haemodynamics. It remains unknown how four-dimensional (4D) acute changes in LV blood flow kinetic energy (KE) affect LV remodeling. We hypothesized that LV blood flow energetics are independently associated with adverse LV-remodeling. Methods In total, 69 revascularised ST-segment elevation MI patients were enrolled. All patients underwent cardiovascular magnetic resonance (CMR) examination within 2 days of the index event and at 3-month. CMR examination included cine, late gadolinium enhancement, and whole-heart 4D flow acquisitions. CMR analysis included: LV volumes, function, infarct size (indexed to body surface area), microvascular obstruction (MVO), two-dimensional, retrospective valve tracking derived mitral inflow metrics, and 4D blood flow KE components (Fig. 1). Adverse LV-remodeling was defined and categorized according to increase in LV end-diastolic volume: 10% (mild), 15% (moderate), and 20% (severe). Results Twenty-four patients (35%) developed mild, 17 patients (25%) moderate, 11 patients (16%) severe LV remodeling. Demographics and clinical history were comparable between patients with/without LV remodeling. In univariable logistic regression analysis, A-wave KE was associated with mild, moderate, and severe LV remodeling (p=0.03, p=0.02, p=0.02, respectively), whereas infarct size was associated with only mild LV remodeling (p=0.02). In multivariable logistic regression analysis, whilst the infarct size and A-wave KE were identified as independent markers for mild LV remodeling (p=0.03, p=0.09, respectively), A-wave KE was the only independent marker regarding moderate and severe LV remodeling (both, p&lt;0.01). In ROC analysis for A-wave KE to be associated with the presence of adverse LV remodeling, the area under the curve was 0.67 for mild (p=0.02), 0.70 for moderate (p=0.01), 0.71 for severe (p=0.03) LV remodeling. Conclusion In patients with STEMI, LV hemodynamics assessment by LV blood flow KE demonstrated an incremental value to predict adverse LV-remodeling. A-wave KE early after acute MI had an independent effect on adverse LV remodeling. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This work was supported by the British Heart Foundation [FS/10/62/28409 to S.P.] and Dutch Technology Foundation (STW), project number 11626 (JW, ME).

Effects of naloxone on systemic and regional hemodynamic responses to exercise in dogs

1988 ◽  
Vol 64 (4) ◽  
pp. 1493-1499 ◽  
Author(s):  
N. Imai ◽  
C. K. Stone ◽  
P. D. Woolf ◽  
C. S. Liang
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Normal Saline ◽  
Adrenocorticotropic Hormone ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Moderate Exercise ◽  
Beta Endorphin ◽  
Developed Pressure

To determine whether endogenous opiates have a role in circulatory regulation during mild to moderate exercise, 11 chronically instrumented dogs were exercised on a treadmill up a 6% incline at 2.5 and 5.0 mph, each for 20 min, after treatment with either the opiate receptor antagonist naloxone (1 mg/kg bolus and 20 micrograms.kg-1.min-1 infusion) or normal saline. Naloxone increased plasma beta-endorphin and adrenocorticotropic hormone at rest but had no effect on resting heart rate, aortic pressure, cardiac output, left ventricular time derivative of pressure (dP/dt) and ratio of dP/dt at a developed pressure of 50 mmHg and the developed pressure (dP/dt/P), or plasma catecholamines. Plasma beta-endorphin and adrenocorticotropic hormone increased during exercise. In addition, graded treadmill exercise produced proportional increases in heart rate, cardiac output, aortic pressure, left ventricular dP/dt and dP/dt/P, and blood flow to exercising muscles, right and left ventricular myocardium, and adrenal glands. However, there were no differences in the circulatory responses to exercise between animals receiving naloxone and normal saline. Thus the endogenous opiate system probably does not play an important role in regulating the systemic hemodynamic and blood flow responses to mild and moderate exercise.

Effects of calcium entry blockade on left ventricular dynamics in exercising dogs

1986 ◽  
Vol 251 (3) ◽  
pp. H656-H663
Author(s):  
R. A. Walsh ◽  
F. X. Cleary ◽  
R. A. O'Rourke
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Coronary Blood Flow ◽  
Left Ventricular ◽  
Calcium Entry ◽  
Peak Exercise ◽  
Beta Blockade ◽  
Lv Function

To study the previously undefined effects of calcium entry blockade on left ventricular (LV) function and coronary blood flow during dynamic exercise we gave intravenous equihypotensive infusions of nifedipine (10 +/- 4 SE micrograms X kg-1 X min-1), diltiazem (60 +/- 8 micrograms X kg-1 X min-1), and verapamil (52 +/- 7 micrograms X kg-1 X min-1) before and after intravenous propranolol (2 mg/kg) to chronically instrumented dogs at rest and while running on a treadmill at 4 and 10 km/h. Prior to beta-blockade, each agent significantly and equivalently (P = NS among drugs) reduced mean arterial pressure during exercise (-13% nifedipine, -8% diltiazem, -15% verapamil at 4 km/h, each P less than or equal to 0.01 vs. exercise alone) but did not significantly alter LV end-diastolic dimension (EDD), heart rate, or cardiac output compared with exercise alone. Only verapamil blunted the positive inotropic response to exercise (LV dP/dtmax decreased 20% at 4 km/h, P less than 0.01 vs. exercise alone). Coronary blood flow was significantly and equivalently increased at rest and during submaximal exercise with each calcium blocker, but this effect was largely offset by propranolol. During exercise after beta-blockade each agent produced significant additional reductions in mean arterial pressure and dP/dtmax at peak exercise but did not alter LVEDD or heart rate compared with results obtained with propranolol alone. Combined beta-blockade and verapamil uniquely diminished myocardial contractility to a greater extent at peak exercise than at rest (dP/dtmax 1,260 +/- 410 peak exercise vs. 1,775 +/- 431 mmHg/s rest, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Injection of isolated mitochondria during early reperfusion for cardioprotection

2009 ◽  
Vol 296 (1) ◽  
pp. H94-H105 ◽  
Author(s):  
James D. McCully ◽  
Douglas B. Cowan ◽  
Christina A. Pacak ◽  
Ioannis K. Toumpoulis ◽  
Haripriya Dayalan ◽  
...  
Keyword(s):  
Infarct Size ◽  
Functional Recovery ◽  
Troponin I ◽  
Left Ventricular ◽  
Cellular Viability ◽  
Area At Risk ◽  
Early Reperfusion ◽  
Ventricular Tissue ◽  
Creatine Kinase Mb ◽  
Developed Pressure

Previously, we demonstrated that ischemia induces mitochondrial damage and dysfunction that persist throughout reperfusion and impact negatively on postischemic functional recovery and cellular viability. We hypothesized that viable respiration-competent mitochondria, isolated from tissue unaffected by ischemia and then injected into the ischemic zone just before reperfusion, would enhance postischemic functional recovery and limit infarct size. New Zealand White rabbits ( n = 52) were subjected to 30 min of equilibrium and 30 min of regional ischemia (RI) induced by snaring the left anterior descending coronary artery. At 29 min of RI, the RI zone was injected with vehicle (sham control and RI vehicle) or vehicle containing mitochondria (7.7 × 106 ± 1.5 × 106/ml) isolated from donor rabbit left ventricular tissue (RI-Mito). The snare was released at 30 min of RI, and the hearts were reperfused for 120 min. Our results show that left ventricular peak developed pressure and systolic shortening in RI-Mito hearts were significantly enhanced ( P < 0.05 vs. RI-vehicle) to 75% and 83% of equilibrium value, respectively, at 120 min of reperfusion compared with 57% and 62%, respectively, in RI-vehicle hearts. Creatine kinase-MB, cardiac troponin I, and infarct size relative to area at risk were significantly decreased in RI-Mito compared with RI-vehicle hearts ( P < 0.05). Confocal microscopy showed that injected mitochondria were present and viable after 120 min of reperfusion and were distributed from the epicardium to the subendocardium. These results demonstrate that viable respiration-competent mitochondria, isolated from tissue unaffected by ischemia and then injected into the ischemic zone just before reperfusion, significantly enhance postischemic functional recovery and cellular viability.

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