Prolonged transient acidosis during early reperfusion contributes to the cardioprotective effects of postconditioning

2007 ◽  
Vol 292 (4) ◽  
pp. H2004-H2008 ◽  
Author(s):  
Masashi Fujita ◽  
Hiroshi Asanuma ◽  
Akio Hirata ◽  
Masakatsu Wakeno ◽  
Hiroyuki Takahama ◽  
...  
Keyword(s):  
Blood Flow ◽  
Infarct Size ◽  
Venous Blood ◽  
Ischemic Myocardium ◽  
Control Group ◽  
Collateral Blood Flow ◽  
Area At Risk ◽  
Early Reperfusion ◽  
Cardioprotective Effects ◽  
Reperfusion Phase

We have previously reported that the prolonged transient acidosis during early reperfusion mediates the cardioprotective effects in canine hearts. Recently, postconditioning has been shown to be one of the novel strategies to mediate cardioprotection. We tested the contribution of the prolonged transient acidosis to the cardioprotection of postconditioning. Open-chest anesthetized dogs subjected to 90-min occlusion of the left anterior descending coronary artery and 6-h reperfusion were divided into four groups: 1) control group; no intervention after reperfusion ( n = 6); 2) postconditioning (Postcon) group; four cycles of 1-min reperfusion and 1-min reocclusion ( n = 7); 3) Postcon + sodium bicarbonate (NaHCO3) group; four cycles of 1-min reperfusion and 1-min reocclusion with the administration of NaHCO3( n = 8); and 4) NaHCO3group; administration of NaHCO3without postconditioning ( n = 6). Infarct size, the area at risk (AAR), collateral blood flow during ischemia, and pH in coronary venous blood were measured. The phosphorylation of Akt and extracellular signal-regulated kinase (ERK) in ischemic myocardium was assessed by Western blot analysis. Systemic hemodynamic parameters, AAR, and collateral blood flow were not different among the four groups. Postconditioning induced prolonged transient acidosis during the early reperfusion phase. Administration of NaHCO3completely abolished the infarct size-limiting effects of postconditioning. Furthermore, the phosphorylation of Akt and ERK in ischemic myocardium induced by postconditioning was also blunted by the cotreatment of NaHCO3. In conclusion, postconditioning mediates its cardioprotective effects possibly via prolonged transient acidosis during the early reperfusion phase with the activation of Akt and ERK.

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 < 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.

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.

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.

Preinfarction Angina and Improved Reperfusion of the Infarct-related Artery

1999 ◽  
Vol 82 (S 01) ◽  
pp. 68-72 ◽  
Author(s):  
Alessandro Sciahbasi ◽  
Eugenia De Marco ◽  
Attilio Maseri ◽  
Felicita Andreotti
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Early Reperfusion ◽  
Vast Number ◽  
Beneficial Effects ◽  
Infarct Related Artery ◽  
Cardioprotective Effects ◽  
Collateral Vessels

SummaryPreinfarction angina and early reperfusion of the infarct-related artery are major determinants of reduced infarct-size in patients with acute myocardial infarction. The beneficial effects of preinfarction angina on infarct size have been attributed to the development of collateral vessels and/or to post-ischemic myocardial protection. However, recently, a relation has been found between prodromal angina, faster coronary recanalization, and smaller infarcts in patients treated with rt-PA: those with preinfarction angina showed earlier reperfusion (p = 0.006) and a 50% reduction of CKMB-estimated infarct-size (p = 0.009) compared to patients without preinfarction angina. This intriguing observation is consistent with a subsequent observation of higher coronary recanalization rates following thrombolysis in patients with prodromal preinfarction angina compared to patients without antecedent angina. Recent findings in dogs show an enhanced spontaneous lysis of plateletrich coronary thrombi with ischemic preconditioning, which is prevented by adenosine blockade, suggesting an antithrom-botic effect of ischemic metabolites. Understanding the mechanisms responsible for earlier and enhanced coronary recanalization in patients with preinfarction angina may open the way to new reperfusion strategies.A vast number of studies, globally involving ≈17,000 patients with acute myocardial infarction, have unequivocally shown that an infarction preceded by angina evolves into a smaller area of necrosis compared to an infarct not preceded by angina (Table 1) (1). So far, preinfarction angina has been thought to have cardioprotective effects mainly through two mechanisms: collateral perfusion of the infarctzone (2-4), and ischemic preconditioning of the myocardium (5-7). Here we discuss a further mechanism of protection represented by improved reperfusion of the infarct-related artery.

scholarly journals Changes in lower extremity blood flow during advancing phases of pregnancy and the effects of special footwear

2017 ◽  
Vol 16 (3) ◽  
pp. 214-219 ◽  
Author(s):  
Marta Gimunová ◽  
Martin Zvonař ◽  
Kateřina Kolářová ◽  
Zdeněk Janík ◽  
Ondřej Mikeska ◽  
...  
Keyword(s):  
Blood Flow ◽  
Venous Blood ◽  
Cross Sectional Area ◽  
Popliteal Vein ◽  
Control Group ◽  
Venous Disease ◽  
Venous Blood Flow ◽  
Sectional Area ◽  
Cross Sectional ◽  
Experimental Group

Abstract Background During pregnancy, a number of changes affecting venous blood flow occur in the circulatory system, such as reduced vein wall tension or increased exposure to collagen fibers. These factors may cause blood stagnation, swelling of the legs, or endothelial damage and consequently lead to development of venous disease. Objectives The aim of this study is to evaluate the effect of special footwear designed to improve blood circulation in the feet on venous blood flow changes observed during advancing phases of pregnancy. Methods Thirty healthy pregnant women participated in this study at 25, 30, and 35 weeks of gestation. Participants were allocated at random to an experimental group (n = 15) which was provided with the special footwear, or a control group (n = 15). At each data collection session, Doppler measurements of peak systolic blood flow velocity and cross-sectional area of the right popliteal vein were performed using a MySonoU6 ultrasound machine with a linear transducer (Samsung Medison). The differences were compared using Cohen’s d test to calculate effect size. Results With advancing phases of pregnancy, peak systolic velocity in the popliteal vein decreased significantly in the control group, whereas it increased significantly in the experimental group. No significant change in cross-sectional area was observed in any of the groups. Conclusions Findings in the experimental group demonstrated that wearing the footwear tested may prevent venous blood velocity from reducing during advanced phases of pregnancy. Nevertheless, there is a need for further investigation of the beneficial effect on venous flow of the footwear tested and its application.

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.

scholarly journals Adenosine A1receptors and mitochondria: targets of remote ischemic preconditioning

2019 ◽  
Vol 316 (3) ◽  
pp. H743-H750 ◽  
Author(s):  
Diamela T. Paez ◽  
Mariana Garces ◽  
Valeria Calabró ◽  
Eliana P. Bin ◽  
Verónica D’Annunzio ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Mitochondrial Function ◽  
Myocardial Infarct ◽  
Remote Ischemic Preconditioning ◽  
Myocardial Infarct Size ◽  
Early Reperfusion ◽  
Endothelial Nitric Oxide ◽  
Isolated Rat ◽  
Reperfusion Phase

Adenosine is involved in classic preconditioning in most species and acts especially through adenosine A1and A3receptors. The aim of the present study was to evaluate whether remote ischemic preconditioning (rIPC) activates adenosine A1receptors and improves mitochondrial function, thereby reducing myocardial infarct size. Isolated rat hearts were subjected to 30 min of global ischemia and 60 min of reperfusion [ischemia-reperfusion (I/R)]. In a second group, before isolation of the heart, a rIPC protocol (3 cycles of hindlimb I/R) was performed. Infarct size was measured with tetrazolium staining, and Akt/endothelial nitric oxide (NO) synthase (eNOS) expression/phosphorylation and mitochondrial function were evaluated after ischemia at 10 and 60 min of reperfusion. As expected, rIPC significantly decreased infarct size. This beneficial effect was abolished only when 8-cyclopentyl-1,3-dipropylxanthine (adenosine A1receptor blocker) and NG-nitro-l-arginine methyl ester (NO synthesis inhibitor) were administered during the reperfusion phase. At the early reperfusion phase, rIPC induced significant Akt and eNOS phosphorylation, which was abolished by the perfusion with an adenosine A1receptor blocker. I/R led to impaired mitochondrial function, which was attenuated by rIPC and mediated by adenosine A1receptors. In conclusion, we demonstrated that rIPC limits myocardial infarct by activation of adenosine A1receptors at early reperfusion in the isolated rat heart. Interestingly, rIPC appears to reduce myocardial infarct size by the Akt/eNOS pathway and improves mitochondrial function during myocardial reperfusion.NEW & NOTEWORTHY Adenosine is involved in classic preconditioning and acts especially through adenosine A1and A3receptors. However, its role in the mechanism of remote ischemic preconditioning is controversial. In this study, we demonstrated that remote ischemic preconditioning activates adenosine A1receptors during early reperfusion, inducing Akt/endothelial nitric oxide synthase phosphorylation and improving mitochondrial function, thereby reducing myocardial infarct size.

Responses to coronary artery occlusion in conscious dogs with selective cardiac denervation

1988 ◽  
Vol 255 (3) ◽  
pp. H525-H533 ◽  
Author(s):  
Y. T. Shen ◽  
D. R. Knight ◽  
S. F. Vatner ◽  
W. C. Randall ◽  
J. X. Thomas
Keyword(s):  
At Risk ◽  
Blood Flow ◽  
Coronary Artery ◽  
Infarct Size ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Conscious Dogs ◽  
Wall Thickening ◽  
Area At Risk ◽  
Cardiac Denervation

The extent to which cardiac denervation alters responses to myocardial ischemia remains controversial. This study compared responses to 24-h coronary artery occlusion (CAO) on measurements of wall thickness (ultrasonic crystals), regional myocardial blood flow (microspheres), and infarct size (triphenyltetrazolium chloride technique) in three groups of conscious dogs with 1) selective posterior left ventricular (LV) wall denervation, 2) selective ventricular denervation, or in 3) intact dogs. After CAO, hemodynamic changes were not different among the three groups. Wall thickening in the ischemic zone became akinetic or paradoxical early after CAO and did not recover in any group over the 24-h monitoring period. Blood flow in the area at risk fell similarly in all groups. Infarct size, as a percentage of the area at risk, was 45 +/- 7% in intact, 48 +/- 6% in posterior LV wall-denervated, and 48 +/- 8% in ventricular-denervated group. There was, however, a lower (P less than 0.05) frequency of arrhythmic beats per minute after 3 h of CAO in the ventricular-denervated group (3.2 +/- 1.4) compared with the intact (11.3 +/- 4.1) or posterior wall-denervated (12.6 +/- 3.2) group. An additional group of ventricular-denervated dogs was studied to determine the effects of sequential, brief 2-min CAO at 2, 4, and 8 wk after denervation. Responses of regional wall thickening to CAO were not affected significantly even after 8 wk following ventricular denervation. Thus, in conscious dogs, neither selective ventricular denervation nor selective denervation of the posterior LV wall improved collateral blood flow, affected regional function favorably, or reduced infarct size after CAO.

Microembolization in pigs: effects on coronary blood flow and myocardial ischemic tolerance

1999 ◽  
Vol 277 (2) ◽  
pp. H533-H542 ◽  
Author(s):  
Frank Grund ◽  
Hilchen T. Sommerschild ◽  
Torstein Lyberg ◽  
Knut A. Kirkebøen ◽  
Arnfinn Ilebekk
Keyword(s):  
At Risk ◽  
Blood Flow ◽  
Infarct Size ◽  
Coronary Blood Flow ◽  
Tissue Perfusion ◽  
Ischemic Tolerance ◽  
Common Finding ◽  
Area At Risk ◽  
Maximal Increase ◽  
Time Flow

Coronary microembolization has been reported to increase coronary blood flow (CBF) through adenosine release. Because adenosine may increase ischemic tolerance against infarction, we tested the hypothesis that myocardial microembolization, a common finding in patients with ischemic heart disease, induces cardioprotection. Additionally, because the use of microspheres is a common tool to measure tissue perfusion, the effects of small amounts of microspheres on CBF were examined. Using anesthetized pigs, we measured CBF with a transit time flow probe on the left anterior descending coronary artery (LAD). In six pigs the relationship between the amount of injected microspheres (0–40 × 106, 15 μm in diameter, left atrial injections) and the effect on CBF was examined. Coronary hyperemia occurred, which was linearly related to the amount of microspheres injected: maximal increase in CBF (%) = 2.8 ± 1.5 (SE) + (5.8 ± 0.7 × 10−7× number of injected microspheres). Because injection of 40 × 106microspheres induced a long-lasting hyperemic response, which could be blocked by 8- p-sulfophenyl theophylline, ischemic tolerance was examined in five other pigs after two injections, each of 40 × 106microspheres, at a 30-min interval. Six control pigs had no injections. Ischemic tolerance was evaluated by measuring infarct size (tetrazolium stain) as the percentage of area at risk (fluorescent particles) after 45 min of LAD occlusion followed by 2 h of reperfusion. Pretreatment by microspheres increased infarct size from 60 ± 3% of area at risk in control animals to 84 ± 6% ( P< 0.05). The injection of microspheres induced a significant hyperemic flow response without causing necrosis by itself. We conclude that microembolization, evoking coronary hyperemia, does not improve but reduces myocardial ischemic tolerance against infarction in pigs.

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