Normal Reperfusion Research Articles

Impact of Total Ischemic Time on No Reflow Phenomenon

Background: Ischemic heart disease, particularly ST-segment elevation myocardial infarction (STEMI), remains a major cause of morbidity and mortality globally. Despite advancements in primary percutaneous coronary intervention (PPCI), the no-reflow phenomenon, characterized by inadequate myocardial reperfusion despite successful vessel recanalization, continues to pose significant challenges, affecting clinical outcomes adversely. Objective: This study aims to investigate the relationship between total ischemic time and the incidence of the no-reflow phenomenon in STEMI patients undergoing PPCI, to identify potential strategies for improving therapeutic outcomes. Methods: Conducted at Hayatabad Medical Complex, Peshawar, this retrospective cohort study included 160 STEMI patients treated over eight months (February to October 2022). We collected data on demographic characteristics, clinical presentation, and outcomes. Inclusion criteria were patients over 18 years, undergoing PPCI within 12 hours of symptom onset, without prior MI, severe bleeding disorders, or previous significant revascularization. Statistical analysis was performed using SPSS 25.0, considering P ≤0.05 as statistically significant. Results: The average total ischemic time was significantly longer in patients experiencing no-reflow (Group I, 7.91 hours) compared to those with normal reperfusion (Group II, 3.41 hours) (P=0.001). Group I also showed higher rates of cardiogenic shock (17.6% vs. 6.8%, P=0.012) and reinfarction (11.8% vs. 2.9%, P=0.010). Mortality was significantly higher in Group I (5.8% vs. 1.9%, P=0.020). Conclusion: Longer total ischemic time is associated with an increased risk of the no-reflow phenomenon and poorer clinical outcomes in STEMI patients. Reducing ischemic time could be crucial in improving reperfusion success and reducing complications post-PPCI.

The effect of the systemic immune-inflammatory index on the no-reflow phenomenon in patients undergoing saphenous vein intervention.

The systemic immune inflammation index (SII), based on lymphocyte, neutrophil, and platelet counts, has been shown to be an independent indicator of no-reflow phenomenon during percutaneous intervention. However, the relationship between SII and no-reflow phenomenon (NRP) that develops after the procedure of saphenous vein grafts is unknown. In this study, we aimed to investigate the relationship between no-reflow phenomenon and SII during percutaneous intervention on saphenous vein grafts. A total of 133 patients who underwent percutaneous intervention for saphenous vein grafts due to acute coronary syndrome between 2019 and 2022 were included in this study. The receiver-operating characteristics (ROC) curve was used to determine the cut-off value of SII to predict the no-reflow. The multivariate regression was used to analyse the correlation between no-reflow and SII. The median value of SII was significantly higher in patients with no-reflow in comparison with normal reperfusion (543 (447, 717) vs. 861 (642, 1272), p < 0.001). The optimal threshold for SII in predicting the no-reflow phenomenon was 613, with sensitivity and specificity of 84% and 66%, respectively. The area under the ROC curve (AUC) was 0.80 (95% CI: 0.73-0.89, p < 0.001). In multivariate analysis, SII ≥ 613 showed an independent predictive value for the no-reflow (OR = 4.02, 95% CI: 1.40-11.57, p < 0.001). Our results showed that high SII levels were independently associated with the development of no-reflow phenomenon in patients presenting with acute coronary syndrome and undergoing percutaneous intervention to the SVG.

The Systemic Immune-Inflammation Index Predicts Impaired Myocardial Perfusion and Short-Term Mortality in ST-Segment Elevation Myocardial Infarction Patients.

In this study, we aimed to evaluate the utility of the immune-inflammation index (SII) in estimating the no-reflow phenomenon and short-term cardiovascular prognosis in patients with ST-segment elevation myocardial infarction (STEMI). 723 consecutive patients with STEMI who underwent primary percutaneous coronary intervention (PCI) were enrolled in our study. The receiver-operating characteristics (ROC) curve was used to determine the cut-off value of SII to predict the no-reflow. The multivariate regression analysis analyzed the correlation between no-reflow and SII. The median value of SII was significantly higher in patients with no-reflow in comparison with normal reperfusion [1466 (939-2409) vs 905 (566-1379), p < .001]. The optimal threshold for SII in predicting the no-reflow phenomenon was 1036, with sensitivity and specificity of 70% and 59%, respectively. The area under the ROC curve (AUC) was 0.71 (95% CI, 0.66-0.75, p < .001). In multivariate analysis, SII ≥ 1036 value showed an independent predictive value for the no-reflow (OR = 0.51, 95% CI: 0.29-0.92, p = .02) and the 30-day cardiovascular mortality (OR = 2.37, 95% CI: 1.34-4.19, p = .003). Our results suggest that higher SII levels are independently associated with the no-reflow phenomenon and 30-day mortality in STEMI patients undergoing primary PCI.

Ultrastructural Characteristics of Myocardial Reperfusion Injury and Effect of Selective Intracoronary Hypothermia: An Observational Study in Isolated Beating Porcine Hearts.

In acute myocardial infarction (AMI), myocardial reperfusion injury may undo part of the recovery after revascularization of the occluded coronary artery. Selective intracoronary hypothermia is a novel method aimed at reducing myocardial reperfusion injury, but its presumed protective effects in AMI still await further elucidation. This proof-of-concept study assesses the potential protective effects of selective intracoronary hypothermia in an ex-vivo, isolated beating heart model of AMI. In four isolated Langendorff perfused beating pig hearts, an anterior wall myocardial infarction was created by inflating a balloon in the mid segment of the left anterior descending (LAD) artery. After one hour, two hearts were treated with selective intracoronary hypothermia followed by normal reperfusion (cooled hearts). In the other two hearts, the balloon was deflated after one hour, allowing normal reperfusion (control hearts). Biopsies for histologic and electron microscopic evaluation were taken from the myocardium at risk at different time points: before occlusion (t = BO); 5 minutes before reperfusion (t = BR); and 10 minutes after reperfusion (t = AR). Electron microscopic analysis was performed to evaluate the condition of the mitochondria. Histological analyses included evaluation of sarcomeric collapse and intramyocardial hematoma. Electron microscopic analysis revealed intact mitochondria in the hypothermia treated hearts compared to the control hearts where mitochondria were more frequently damaged. No differences in the prespecified histological parameters were observed between cooled and control hearts at t = AR. In the isolated beating porcine heart model of AMI, reperfusion was associated with additional myocardial injury beyond ischemic injury. Selective intracoronary hypothermia preserved mitochondrial integrity compared to nontreated controls.

P3591Residual atherothrombotic burden after primary percutaneous coronary intervention and myocardial reperfusion - An optical frequency domain imaging study

Abstract Background The clinical significance of residual in-stent atherothrombotic burden (ATB) after primary percutaneous coronary intervention (PCI) remains unclear. Several methods of ATB quantification using optical frequency domain imaging (OFDI) exist. Objectives We aimed to assess the relationship between residual ATB after primary PCI measured in OFDI using different methods and myocardial blush grade (MBG). Methods We prospectively included 60 ST-elevation myocardial infarction patients pre-treated with aspirin and ticagrelor. OFDI volumetric quantification using planimetry (with intervals every frame or every millimeter) and semi-quantitative score were used to determine ATB. Patients were divided into two groups according to final MBG 3 or &lt;3. Results MBG 3 was identified in 28 (46%) patients. Altogether, 13318 OFDI cross-sections were analyzed. The mean ATB was 10.08±5.21%. ATB was lower in patients with normal final MBG compared to those with impaired MBG, regardless of the method used (8.15±5.58 vs 11.77±4.28%; p=0.007 for quantification per frame; 7.8±5.19 vs 11.07±4.07%; p=0.009 for quantification per mm and 11.21±11.75 vs 22.91±17.35; p=0.003 for the semi-quantitative thrombus score, respectively). Table 1. Post stenting OFDI findings OFDI measures All Final Blush &lt;3 Final Blush 3 p n=60 (100%) n=32 (53%) n=28 (47%) Stent volume (mm3) 219.42±135.76 226.08±168.69 211.82±86.57 0.68 Evaluation per frame Atherothrombotic volume (mm3) 21.66±16.81 25.83±18.86 16.89±12.83 0.035 Atherothrombotic burden (%) 10.08±5.21 11.77±4.28 8.15±5.58 0.007 Evaluation per millimeter Atherothrombotic volume (mm3) 20.71±16.16 24.57±18.15 16.29±12.43 0.042 Atherothrombotic burden (%) 9.5±4.88 11.07±4.07 7.8±5.19 0.009 Thrombus score 17.45±16 22.91±17.35 11.21±11.75 0.003 Optical frequency domain imaging example Conclusion Residual post-stenting ATB remains substantial after primary PCI in STEMI patients, even when pre-treated with ticagrelor and aspirin. Mostly, it appears as an important surrogate of clinical outcome as patients with normal myocardial reperfusion presented lower residual ATB.

High-sensitivity C-reactive protein and long term reperfusion success of primary percutaneous intervention in ST-elevation myocardial infarction

AimsIn STEMI patients, success of reperfusion of primary PCI predicts cardiac remodeling and clinical outcome. This success may depend on inflammation. We aimed to investigate the association between inflammation and reperfusion success, left ventricular function and long-term mortality in STEMI patients. MethodsIn 376 consecutive STEMI patients of the GIPS-III trial hs-CRP levels were measured at baseline, 2weeks, 7weeks and 4months post-PCI. Myocardial blush grade was used to determine success of myocardial reperfusion. In multivariate models sex, age, hs-CRP levels at baseline, NT-proBNP levels at baseline, ischemia time, heart rate, TIMI flow, and CK, CKMB and troponin AUC were included. Follow-up was complete until 4months. ResultsBaseline hs-CRP levels were 2.1mg/l (IQR 0.5–4.2mg/l). hs-CRP levels were associated with impaired reperfusion (OR 1.239, 95% CI 1.006–1.527) and remained higher compared to patients with normal reperfusion up to 2months after PCI (hs-CRP 1.9mg/l (IQR 0.9–3.7mg/l) versus 1.5mg/l (IQR 0.7–2.7mg/l), p=0.041). In multivariate analysis baseline hs-CRP levels remained independently associated with impaired reperfusion. In patients with impaired reperfusion, hs-CRP and NT-proBNP levels remained higher during 4months of follow-up. No correlation was observed between hs-CRP at baseline and left ventricular function at 4months. The number of events was small and we observed no differences in mortality. ConclusionIncreased hs-CRP levels at presentation are associated with impaired microvascular reperfusion after PCI in STEMI patients and remain higher until 2months follow-up.

QRS Complex Duration is a Marker of Reperfusion in Patients Presenting with Acute ST Segment Elevation Myocardial Infarction

Background: Acute myocardial ischemia decreases electrical conduction velocity through the ischemic myocardium, the aim of the study is to evaluate the value of the change in QRS complex duration as a marker of reperfusion in patients presenting with ST segment elevation myocardial infarction. Methods: The study included 100 patients presented with ST segment elevation myocardial infarction, 50% treated with fibrinolysis and 50% with primary Percutaneous intervention, all patients were subjected to 12 lead electrocardiography with measurement of QRS complex duration (in millisecond) on admission, sixty and ninety minutes post reperfusion , coronary angiography was done to all patients and they were divided into two groups according to myocardial blush grade, group A (5 5%) with normal reperfusion (grade 2 and 3) and group B (45%) with impaired reperfusion (grade 0 and 1). Results: We found that the admission QRS duration didn’t differ in the two groups (p=0.859), and QRS complex duration was found to be significantly shorter in group A at both 60 and 90 min post reperfusion (pE‚0.001 for both), and found a strong positive correlation between myocardial blush grade and QRS complex narrowing at both 60 min and 90 min post reperfusion respectively (r=0.731, pE‚0.001 and r=0.739, pE‚0.001). A cut off 10 msec was determined to be the best QRS complex narrowing duration for prediction of reperfusion at both 60 and 90 min post reperfusion with 100% sensitivity, and a specificity of (43.64% and 58.18%) at 60 min and 90 min post reperfusion respectively. Conclusion: QRS duration changes post reperfusion is strongly correlated to myocardial reperfusion in patients presenting with ST segment elevation myocardial infarction.

A Comparison of the Performance of Myocardial Videodensitometry, Tissue Velocity Imaging and Tissue Tracking in Discrimination Between ST-Segment Elevation Ischemic Reperfusion Injury and Normal Reperfusion State After Non-Beating Cardiac Operation.

Background:The timely diagnosis of presence or absence of reperfusion injury after cardiac operation is critical for the patient’s outcome. Whether transesophageal echocardiography (TEE) acquisition of regional grayscale intensity (TI), velocity, and displacement (D) after cardiac operation can discriminate between patients with ST-segment elevation ischemic reperfusion injury (STEIRI) and normal reperfusion state remains unknown.Objectives:In this study, we investigated whether these parameters can effectively reflect the situation of ST-segment elevation ischemic reperfusion injury (STEIRI) in patients after cardiac operation and which has a higher performance of discrimination between patients with and without STEIRI.Patients and Methods:The maximal and minimal grayscale intensity in the cardiac cycle [TI (max), TI (min)], the difference of TI (max) and TI (min) [TI (max-min)], the cyclic variation index of TI [TI (CVI)], the systolic velocity (Vs), the early diastolic velocity (Ve), the late diastolic velocity (Va) and the peak displacement in the cardiac cycle (D) at the lateral side of the mitral annulus were measured and compared between patients with and without STEIRI. The performance of these parameters in discriminating between patients with and without STEIRI was analyzed.Results:Compared with the patients without STEIRI, the patients with STEIRI had significantly smaller TI (max-min), TI (CVI), Vs, Ve, Va and D (P<0.05). With the use of these parameters as the criteria to distinguish patients with STEIRI from patients without STEIRI, the areas under the receiver operating characteristic curve were 0.86 for TI (max-min), 0.99 for TI (CVI), 0.89 for Vs, 0.71 for Ve, 0.85 for Va and 0.82 for D. For the best cut-off value of TI (CVI) of less than 34.45%, the sensitivity, specificity and accuracy for the prediction of patients with STEIRI were 94.74%, 97.05%, and 96.22%, respectively.Conclusion:The myocardial grayscale intensity, velocity and displacement can effectively reflect the situation of STEIRI in patients after cardiac operation, and TI (CVI) has a higher performance in discriminating between patients with and without STEIRI.

The evaluation of cerebral function by diffusion weighted imaging after norepinephrine-induced hypertensive perfusion therapy in pig model of cardiac arrest

To evaluate the changes in cerebral function of pigs with cardiac arrest (CA) after recovery of spontaneous circulation (ROSC) after hypertension perfusion therapy induced by norepinephrine (NE). Ventricular fibrillation (VF) was induced by electrical stimulation, and standard cardiopulmonary resuscitation (CPR) was performed after VF for 4 minutes. The pigs with successful ROSC were randomly divided into two group, each n=5. The pigs in the hypertensive reperfusion group were given with NE immediately to maintain the mean arterial pressure (MAP) at 130% before VF for 4 hours; MAP of the pigs in normal reperfusion group was maintained for 4 hours as baseline. The changes in hemodynamics were observed for 4 hours in both groups. Cerebral cortex was scanned with diffusion weighted imaging (DWI) before VF and 1 hour and 3 hours after ROSC, and the dynamic changes in brain functional imaging were observed. Twenty-four hours after ROSC, brain biopsy were collected and examined after hematoxylin and eosin staining (HE). Compared with the normal reperfusion group, heart rate (HR), MAP, cardiac output (CO) and coronary perfusion pressure (CPP) in the hypertensive reperfusion group showed a tendency to increase (ROSC 30 minutes HR: 167±8 bpm vs. 140±15 bpm, ROSC 1 hour MAP: 131±9 mm Hg vs. 108±10 mm Hg, ROSC 1 hour CO: 4.9±0.1 L/min vs. 3.4±0.5 L/min, ROSC 2 hours CPP: 118±12 mm Hg vs. 88±1 mm Hg, P<0.05 or P<0.01). There was no obvious abnormality as shown by DWI before and after resuscitation, and the apparent diffusion coefficient (ADC) showed a tendency to decrease after resuscitation in both groups. The ADC in the normal reperfusion group was decreased more than that in the hypertensive reperfusion. Pathological study showed that the protective effect of the hypertensive reperfusion on brain tissue was better than that of the normal reperfusion group. Hypertensive reperfusion can produce hemodynamic changes, and an increase in cerebral blood flow, thus it produces a protective effect on brain to promote the recovery of neurological function in pigs with CA after resuscitation.

Effects of mild hypothermia on proNGF apoptosis pro-signal following cerebral ischemia and reperfusion

Objective To observe the expressional changes of pro nerve growth factor(proNGF)apoptosis pro-signal factors after cerebral ischemia and reperfusion and discuss the protective effect of mild hypothermia on the brain injury. Methods The randomly chosen female SD rats weighing(220±10)g were divided into normal control group(Group A),cerebral isehemia and reperfusion group (Group B)and mild hypothermia group(Group C).Groups B and C were divided into 3,6 and 9 hours subgroups(eight rats per group).TUNEL methods was used to detect the apoptotic cells in the cortex after cerebral ischemia and reperfusion and treatment with mild hypothermia.The reverse transcription polymerase chain reaction(RT-PCR)was used to detect the expression changes of proNGF,Sortilin and P75gene in the cortex. Results (1)The apoptotic cells were increased with time in the Group B(P<0.05)and were more than those in the Group C in the same time point(P<0.05).(2)There found expression of all factors at all time points in three groups,which was increased with time(P<0.05).(3)The content of every factor at each time point in the Group C was less than that in the Group B(P<0.05). Conclusions (1)Mild hypothermia can decrease the apoptosis after ischemia and reperfusion injury.(2)The cell apoptosis induced by proNGF plays a very important role in the COUrse of cerebral ischemia and reperfusion injury.(3)Mild hypothermia can decrease the expression of apoptosis pro-signal to alleviate the cell apoptosis and protect the brain from ischemia and reperfusion. Key words: Reperfusion injury,brian; Hyhothermia,induced; Nerve growth factor; Apoptosis

Relationship Between Collateral Circulation and Successful Myocardial Reperfusion in Acute Myocardial Infarction: A Subanalysis of the PREMIAR Trial

The aim of this study was to determine whether the presence of collateral circulation had a beneficial effect following primary angioplasty. In all, 114 patients who underwent primary angioplasty were included. Patients with collateral circulation had lower basal ST-segment deviation (P = .004), white cell count ( P = .001), peak creatine kinase (P = .001), and regional wall motion score values (P = .03) than patients without collateral circulation. After the procedure, the group with collaterals was associated with higher rates of normal myocardial blush, complete ST resolution, and shorter time to stable ST-recovery. Multivariable logistic analysis identified the presence of collateral circulation as independent predictor of normal myocardial blush (adjusted odds ratio = 3.98, 95% confidence interval, 1.12-14.09; P = .033) and rapid reperfusion (time to stable ST-segment recovery <7 minutes, adjusted odds ratio = 4.0, 95% confidence interval, 1.57-10.20; P = .004). The presence of collateral circulation has a protective effect on infarct size, resulting in faster reperfusion.

Reperfusion capacity of the femur head after ischemia--an experimental study

The aim of this study was to evaluate bone blood flow of the proximal femur during experimentally induced ischemia and to document the ability of epiphyseal and metaphyseal reperfusion. 11 pigs (danish landrace) were used to investigate the effect of tamponade by increased joint pressure (Dextran 70) on the perfusion of the femoral head. Additional 8 pigs were used as control. The blood flow in the hip joint was studied by means of the microsphere technique. The flow was determined before, during and after intraarticular pressure increase. With the "radioactive tracer microsphere"-method the blood flow of the epiphysis, metaphysis and proximal femoral corticalis could be measured. In the epiphyseal femoral head the initial blood flow rate, 11.7 ml/min/100 g, was not significant different from that of the control side (11.1 ml/min/100 g). The blood flow decreased in the ischemic phase to 1.8 ml/min/100 g followed by reperfusion to 13.5 ml/min/100 g (p < 0.01). The bone blood flow of reperfusion was not significant different from that of the initial blood flow rate but in 2 cases a "blow out" of the epiphyseal bone blood flow was seen. The proximal femoral metaphysis showed the highest of the measured intraosseous flow rates (17.9 resp. 23.3 ml/min/100 g). During ischemia and reperfusion of the epiphysis bone blood flow of the metaphysis remained the same. The proximal femoral corticalis showed the lowest of the measured intraosseous flow rates. The operated (10.1 ml/min/100 g) and contralateral hip side (11.7 ml/min/100 g) showed no significant differences in the initial blood flow rate. During ischemia and reperfusion the blood flow of the proximal corticalis showed no significant difference to the initial blood flow corresponding to the metaphysis. Our study demonstrates disturbances of the circulation of different regions of the femoral head during intraarticular pressure increase and following pressure decrease of the growing pig. 2 "blow outs" document a vulnerable proximal epiphysis already after a 6-hour ischemia. Additional minor "bone quality" in cases of certain diseases (kidney transplantation, leukemia) and special administration of drugs (corticosteroids) seem to create an additional vulnerability of the proximal femoral head. The experiment proves to be a reliable model for decreasing the blood flow of the growing epiphysis temporarily and to document the beginning of normal reperfusion. With this model it is possible to examine the vulnerability of the epiphyseal perfusion after different diseases and under the influence of different medication.

Microcirculatory dysfunction in ST-elevation myocardial infarction: cause, consequence, or both?

Despite advancements over the past years, normal reperfusion at the myocardial level is not achieved in approximately every other patient with ST-elevation myocardial infarction. In the current work, we aimed at reviewing the role of the coronary microcirculation in the development and outcome of this acute coronary syndrome entity. A PubMed/Medline search was performed with the key words acute coronary syndrome, acute myocardial infarction, coronary artery disease, endothelial dysfunction, microcirculation, and reperfusion. The synthesis of the information points to myocardial microcirculatory dysfunction as a consequence of a primary epicardial event, based on the vulnerable plaque concept. As an alternative theory, microcirculatory dysfunction may contribute to the clinical course of the acute coronary event, based on the vulnerable patient concept. The pros and cons of these two viewpoints are to be discussed and their influence on patient management is to be considered. Microcirculatory dysfunction in ST-elevation myocardial infarction can be cause, consequence or both according to non-traditional and traditional concepts.

Controlled low-pressure perfusion at the beginning of reperfusion attenuates neurologic injury after spinal cord ischemia

Paraplegia caused by spinal cord ischemia remains a serious complication after surgical repair of thoracoabdominal aortic aneurysms. This study tests the hypothesis that controlled low-pressure perfusion at the beginning of reperfusion can attenuate neurologic injury of the spinal cord after transient ischemia. Spinal cord ischemia was accomplished in rabbits by occlusion of the infrarenal aorta with a balloon catheter for 25 minutes. In the normal reperfusion group, reperfusion was completely restored immediately after ischemia, whereas perfusion pressure was controlled between 45 and 55 mm Hg during the first 10 minutes followed by complete reperfusion in the low-pressure reperfusion group. Functional evaluation with the Tarlov score during a 14-day observation period, histopathologic assessment of the lumbar spinal cord, and measurements of malondialdehyde levels and amyloid precursor protein immunoreactivity were performed. Neurologic impairment was remarkably attenuated in the low-pressure reperfusion group (compared with the Tarlov scores of the normal reperfusion group, P < .05 at day 2; P < .01 at days 1, 7, and 14). Compared with the normal reperfusion group, malondialdehyde levels were significantly lower in the low-pressure reperfusion group (P < .05), and the large motor neurons of the low-pressure reperfusion group were preserved to a much greater extent (P < .05). White matter injury of the low-pressure reperfusion group was also markedly attenuated as evidenced by reduction of vacuolation area of the white matter (P < .05) and decrease of the amyloid precursor protein immunoreactivity (P < .05). Reperfusion initiated with low-pressure perfusion exerts neuroprotective effects on the spinal cord against ischemia/reperfusion injury.

Effects of Ischemic Preconditioning and Propofol on Cardiac Function and Coronary Flow following Cold Cardioplegia and Reperfusion in Isolated Rat Heart

Background: The interaction between ischemic preconditioning (IPC) and propofol-induced cardioprotective effects during prolonged cold ischemia has not been studied yet. The purpose of this study is to investigate the effects of ischemic preconditioning and propofol on cardiac function and the development of endothelial injury after 4 hours of cold cardioplegia and reperfusion. Methods: After suspension of the isolated heart on the Langendorff perfusion system, we took a stabilizing period for 15 minutes, perfusion period for 15 minutes, global cold (4) ischemic period for 4 hours, and then reperfusion period for 60 minutes. There were 4 groups: (1) CONTROL group, no intervention; (2) IPC group, two 2-minute total coronary clusions interspaced with 5 minutes of normal reperfusion; (3) PROPOFOL group, propofol (2M) was infused during reperfusion period; (4) BOTH group, ischemic preconditioning and postischemic propofol treatment group. The measurements of cardiac performances, such as left ventricular developed pressure (LVDP), rate of ventricular pressure generation (dp/dt), and heart rate (HR) was obtained at pre- and postischemic periods. For the evaluation of endothelial injury during reperfusion period, coronary flow responses to bradykinin were tested. Infarct size was measured using the triphenyl tetrazolium stain. Results: IPC, PROPOFOL, and BOTH groups showed better outcome of LVDP, dp/dt, HR, and flow responses to bradykinin than CONTROL group did. But there is no statistically significant difference in variables among the three groups. Conclusions: Ischemic preconditioning and postischemic propofol have cardioprotective effect respectively but no additive effect after 4 hours cold cardioplegia and reperfusion.

Adenosine A1 receptor activation reduces myocardial reperfusion effects on intrinsic cardiac nervous system.

The intrinsic cardiac nervous system is the final common integrator of regional cardiac function. The ischemic myocardium modifies this nervous system. We sought to determine the role that intrinsic cardiac neuronal P(1) purinergic receptors play in transducing myocardial ischemia and the subsequent reperfusion. The activity generated by ventricular neurons was recorded concomitant with cardiac hemodynamic variables in 44 anesthetized pigs. Regional ventricular ischemia was induced by briefly occluding (30 s) the ventral interventricular coronary artery distal to the arterial blood supply of identified ventricular neurons. Adenosine (100 microM) was administered to these neurons via their local arterial blood supply during or immediately after transient coronary artery occlusion. Occlusion was also performed following local administration of adenosine A(1) [8-cyclopentyl-1,3-dipropylxanthine (DPCPX)] or A(2) [3,7-dimethyl-1-propargylxanthine (DMPX)] receptor blocking agents. The activity generated by ventricular neurons was modified by transient coronary artery occlusion and the subsequent reperfusion (||Delta|| 112 +/- 14 and 168 +/- 34 impulses/min, respectively; P < 0.01 vs. preischemic states). Locally administered adenosine attenuated neuronal responses to reperfusion (-75%; P < 0.01 compared with normal reperfusion) but not ischemia. The neuronal stabilizing effects that adenosine elicited during reperfusion persisted in the presence of DMPX but not DPCPX. It is concluded that activation of neuronal adenosine A(1) receptors stabilizes the intrinsic cardiac nervous system during reperfusion.

Multicenter, dose-ranging study of efegatran sulfate versus heparin with thrombolysis for acute myocardial infarction: The Promotion of Reperfusion in Myocardial Infarction Evolution (PRIME) trial

Background Adjunctive therapies that increase the incidence of normal reperfusion after thrombolysis for acute myocardial infarction (MI) could enhance clinical outcomes. Direct thrombin inhibitors may offer an advantage over standard adjunctive therapies. Methods We randomized 336 patients with acute MI at 33 sites to receive 1 of 5 doses of efegatran sulfate, a direct thrombin inhibitor, or heparin for 72 to 96 hours, both with accelerated alteplase and aspirin. The primary end point was the incidence of thrombolytic failure (death, reinfarction, or TIMI grade 0–2 flow in the infarct artery from 90 minutes to discharge or 30 days, whichever occurred earlier). Results Significantly more patients randomized to efegatran had evidence of heart failure at admission. The lowest-dose efegatran arm was terminated at 15 patients because of unacceptably increased thrombolytic failure. The primary end point occurred in 53.0% of patients treated with heparin, in 53.8% of patients treated with efegatran overall (P =.90), and in 55.4% of patients given intermediate-dose efegatran (P =.74). These findings were unaffected after adjustment was done for baseline differences. Most bleeding was minor; major bleeding and the use of blood transfusions did not differ significantly by treatment. Three patients in the high-dose efegatran group had intracranial hemorrhage, as did 1 patient in the heparin group. Continuous ST monitoring showed a shorter time to recovery for the efegatran group (median 107 minutes) compared with the heparin group (154 minutes; P =.025). Conclusions Efegatran sulfate appeared to offer no clear advantage over heparin as an adjunct to thrombolysis for acute myocardial infarction, although there may be a modest improvement in time to reperfusion. (Am Heart J 2002;143:95-105.)

Reduction of endothelial injury after hypothermic lung preservation by initial leukocyte-depleted reperfusion

Objectives: Leukocyte depletion has been shown to ameliorate the effects of reperfusion injury in many organ systems. The aim of this study was to investigate the effects of leukocyte depletion on functional and endothelial markers of pulmonary performance after cold ischemic injury. Method: Groups of 6 rat lungs were flushed with University of Wisconsin solution and then stored at 4°C for 4 hours. They then underwent sanguine reperfusion for 30 minutes, during which time functional measures (gas exchange, pulmonary artery, and airway pressures) were made and after which the lungs underwent estimation of endothelial permeability by measurement of the capillary filtration coefficient (in grams per centimeter of water per minute per grams of wet lung tissue) by a gravimetric technique. Four groups were studied: group 1 underwent no reperfusion, group 2 underwent 30 minutes of reperfusion, group 3 underwent 30 minutes of leukocyte-deplete reperfusion with an in-line leukocyte filter (PALL), and group 4 underwent 10 minutes of leukocyte-depleting reperfusion followed by 20 minutes of normal reperfusion. Results: The capillary filtration coefficient increased between group 1 and group 2 animals (1.05 ± 0.32 to 3.07 ± 0.47 [mean ± SEM]; P <.01). Complete leukocyte depletion caused the greatest diminution in the capillary filtration coefficient (0.392 ± 0.07, P <.001), but initial leukocyte depletion (group 4) also showed a significant diminution (0.74 ± 0.3, P <.01). Complete or initial leukocyte depletion caused no significant change in functional measures of pulmonary performance. Complete leukocyte depletion produced less pulmonary leukostasis, as assessed by means of myeloperoxidase activity. Conclusion: Initial and continued leukocyte depletion are associated with amelioration of reperfusion-induced endothelial injury after cold ischemic injury. (J Thorac Cardiovasc Surg 2000;120:47-54)

Decreased Expression of Tissue Inhibitor of Metalloproteinase 1 in Stunned Myocardium

Ultrastructural studies of stunned myocardium have shown disorganization and loss of extracellular collagen and increased collagenase activity early after ischemia and reperfusion. The interplay between matrix metalloproteinase 1 (MMP-1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) regulates the turnover of cardiac extracellular matrix fibrillar collagens. However, the gene expression of MMP-1 and TIMP-1 in stunned myocardium is not known. Here, we determined whether altered expression of MMP-1 and TIMP-1 occurs in globally stunned hearts. An isolated nonworking rabbit heart preparation, perfused with a bovine erythrocyte suspension in modified Krebs solution, was used. Two groups were studied: the stunned group was subjected to 20 min of normothermic global ischemia followed by 120 min of normal reperfusion (n= 8), and the control group underwent 140 min of uninterrupted perfusion (n= 7). The developed pressures at the end of reperfusion for ischemic and control hearts were 67.0 ± 2.73 and 83.1 ± 1.52 mm Hg (P< 0.006) respectively. Ribonuclease protection assays of total left ventricular RNA using riboprobes for MMP-1, TIMP-1, and 18S rRNA were performed. A significant decrease (twofold,P< 0.03) in TIMP-1 gene expression was found in the stunned hearts, while MMP-1 mRNA expression was unchanged. Thus, in early stunning, the decrease in TIMP-1 expression could tip the balance favoring enhanced metalloproteinase activity, promoting collagen turnover, and initiating extracellular matrix remodeling. This may contribute to delayed recovery from myocardial stunning.

Time Course of Leukocyte Adhesion to Endothelium in Ischemia–Reperfusion

Adhesion of leukocytes (L) to microvascular endothelium (E) is a required step in the L–E interaction leading to tissue injury in ischemia–reperfusion. To assess the optimum period for therapy aimed at ameliorating negative effects of this required step, we investigated the time course of L–E adhesion in the hamster cheek pouch using 2 hr of ischemia and 1 hr of reperfusion in our model of I–R injury (Am. J. Physiol.261: 1626, 1991). Leukocytes adhering (stationary for ≥30 sec) to postcapillary venules (15–30 μm in diameter) were counted after labeling with acridine orange. Prior to the induction of ischemia, there were no significant differences in the number of adherent leukocytes in each area chosen for study (1.9 ± 0.6 vs 2.0 ± 0.3; mean number of leukocytes/100-μm vessel length ± SD). After 10 and 20 min of reperfusion there was no significant difference in leukocyte adhesion in the ischemic area relative to the control (2.7 ± 0.5 vs 2.8 ± 0.8, and 5.3 ± 2.8 vs 2.4 ± 0.6, respectively). Leukocyte adherence increased significantly after 30 min of reperfusion and remained elevated at 1 hr of reperfusion in the postischemic area relative to the nonischemic control area (7.8 ± 1.3 vs 3.6 ± 0.6, and 8.3 ± 0.8 vs 4.1 ± 0.6, respectively;P< 0.01). Leukocyte adhesion in the postischemic area after 30 min reperfusion was not significantly different from the adhesion at the end of 1 hr reperfusion. These data suggest that (1) peak leukocyte adhesion occurs after 30 min of normal reperfusion and (2) postischemic therapeutic intervention may be most beneficial when instituted within this early time period.