Total Duration Of Ischemia Research Articles

Органосохраняющие операции при сложных опухолях почек

Aim To analyze the results of nephron sparing surgery (NSS) in patients with complex and large kidney tumors (R.E.N.A.L. 10-12). Materials and methods A total of 361 interventions for kidney neoplasm were performed from 2013 to 2018, including 207 (57,34%) NSS. The complex renal tumors were defined using R.E.N.A.L. nephrometry score. In 44 patients, tumors had a R.E.N.A.L. score of 10-12 (21,26%). Postoperative complications were classified using Clavien-Dindo system. Estimated glomerular filtration rate (eGFR) was assessed before operation and on the 1st-3rd postoperative day. Results Among tumors with R.E.N.A.L. score of 10-12, T1a, T1b and T2 stages were found in 13,64%, 70,45% and 15,91% cases, respectively. Robot-assisted partial nephrectomy was performed in 95%, while laparoscopic procedure was done in 5% of patients. Median operation time was 190 [170; 215] min, while median blood loss was 150 [100; 300] ml. There were 2 intraoperative complications (4,55%). Intraoperative complications were recorded in 2 (4.55%) patients. Postoperative complications developed in 22.73% of cases, including 3 patients with Grade I-II (6.82%) and 7 patients with Grade III complications (15.91%). Total, segmental ischemia and zero-ischemia was used in 31 (70.45%), 12 (27.27%) and 1 (2.27%) patients, respectively. The median duration of total ischemia was 20.0 [17; 25] min. A positive surgical margin was found in 1 (2.27%) patient. In 46.51% of cases, there was no decrease in eGFR in the early postoperative period. In 28% of patients, eGFR decreased by more than 20%. On average, GFR declined by 6.01%. Conclusion NSS in patients with complex renal tumors is an effective alternative to radical nephrectomy, which provides an acceptable level of postoperative complications, with moderate decrease in eGFR and low rate of positive surgical margin.

P6423Cardioprotective effect of metoprolol in myocardial ischemic/reperfusion injury: the role of total ischemic time

Abstract Background Metoprolol administration before reperfusion has shown relevant cardioprotective effect in the AMI in preclinical setting. However, the translation to clinical arena has controversial results. The time at drug administration in the context of total duration of ischemia have been pointed as fundamental aspects to be studied. Purpose evaluate the cardioprotective effect of metoprolol administration regarding to the total time of ischemia, using a swine model of reperfused AMI. Methods 50 pigs were subjected to 3 temporary protocols of left anterior descending (LAD) coronary artery occlusion followed by reperfusion. 30 pigs undergoing 40 minutes of ischemia (T40) were randomized 2:1 to intravenous placebo or metoprolol administrated 20 minutes after LAD occlusion.10 pigs undergoing 20 minutes of ischemia 20 (T20) and 10 pig undergoing 60 minutes of ischemia 60 (T60) were randomized 1:1 to intravenous placebo or metoprolol. Before reperfusion a CT study was performed to stablish the area at risk (AAR). CMR was performed at 7 and 45 days after AMI. Results 48 subjects comprised the 7-day CMR follow-up (1 dead in the metoprolol T40,1 dead in the placebo T40) while 41 subjects comprised the 45-day CMR follow-up (5 deceases in the placebo T40 group, and 2 in the placebo T60 group). AAR was similar among groups (Table 1, Panel B). At 7-day follow-up, IS washigher in the placebo groups as compared to the metoprolol groups, but only reach significant difference in the T40 (29,67% vs. 22,85%, p=0.04, Table 1, Panel A). LVEF measured at 45-day follow-up was higher in the metoprolol groups vs the control groups, but the differences were statistically significance in the T40 (32,76% vs 39,68% p=0.04, Panel C). Table 1 20 mins. Ischemia (T20) 40 mins. Ischemia (T40) 60 mins. Ischemia (T60) P PLACEBO METOPROL P value PLACEBO METOPROL P value PLACEBO METOPROL P value AAR 32 (28.14–37.89) 33.41 (28.12–38.32) 0.82 32.99 (29.25–35.83) 31.42 (26.94–37.83) 0.72 33.28 (29.68–41.14) 33.93 (28.17–40.69) 0.80 0.98 IS 1.96 (0.92–3.61) 0 (0–0.65) 0.063 29.67 (27.23–35.35) 22.85 (14.53–28.10) 0.042 36.21 (33.55–40.91) 33.78 (39.36–35.39) 0.31 <0.001 LVEF 54.36 (49.75–58.97) 55.34 (53.14–60.88) 0.66 32.76 (26.91–36.10) 39.68 (35.45–45.28) 0.023 26.13 (22.40–31.25) 32.99 (31.32–35.19) 0.071 <0.001 Values are median (interquartile range). Bold indicates statistical significance. AAR = Area at Risk (% of Left ventricular). IS = Infartc Size (% of Left ventricular). LVEF = Left ventricular ejection fraction (%). Conclusions Metoprolol administrated early before reperfusion reduced IS and improved medium-term LVEF compared to placebo. But only T40 receiving metoprolol shownsignificant protection vs placebo. These findings suggest a relevant effect of metoprolol ischemic/reperfusion injury, but depending on the total ischemic time, establishing a potential temporary cardioprotection opportunity window.

Influence of Renin-Angiotensin System Blockers on Graft Function in Retrospective Analysis of Pairs of Renal Transplant Recipients From the Same Donor

BackgroundRenin-angiotensin system (RAS) blocking agents efficiently control hypertension in renal transplant recipients (RTRs), and reduce proteinuria and post-transplant erythrocytosis. A beneficial effect on the retardation of the long-term decline in renal function has not yet been demonstrated. The aim of the study was to evaluate the effects of RAS blockade on allograft function. MethodsIn order to minimize donor variability and bias, 33 pairs of RTRs receiving grafts from the same donor were included into the retrospective analysis. A total of 66 RTRs were enrolled in which 1 patient from the pair used an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for a minimum period of 60 months (RAS[+]) and the second one did not use it at all (RAS[-]). ResultsThere were no differences between RAS(+) and RAS(-) subjects in terms of age, body mass index, mismatches number, duration of total ischemia, episodes of cytomegalovirus infections, acute rejections, or immunosuppressive treatment. Significantly, more RAS(+) patients presented with diabetes and cardiovascular complications. Among RAS(+) patients, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were used in 28 (84.84%) and 5 (15.15%) patients in a mean dose of 23.03 ± 16.83% and 30 ± 11.18% of their maximum doses, respectively. There were no significant differences in estimated glomerular filtration rate changes (−0.37 ± 12.68 vs 2.54 ± 20.76 mL/min) and serum creatinine changes (0.05 ± 0.39 vs 0.14 ± 0.79 mg/dL) between RAS(+) and RAS(-) patients during the 60 months follow-up. ConclusionAgents inhibiting the RAS did not significantly affect graft function in RTRs during 60 months of observation.

Cardioprotection of the enkephalin analog Eribis peptide 94 in a rat model of ischemia and reperfusion is highly dependent on dosing regimen and timing of administration

Eribis Peptide 94 (EP94) is an enkephalin analog with cardioprotective properties in ischemia and reperfusion. The aim of the present study was to define the optimal timing and dosing of the administration of EP94 during ischemia and reperfusion in a rat model. 172 anesthetized and mechanically ventilated male Sprague–Dawley rats were randomly assigned to different administration protocols of EP94 and subjected to 30 or 40min of coronary artery occlusion followed by 2h of reperfusion. EP94 was administered intravenously at different doses and time intervals. Area at risk (AAR) and infarct size (IS) were determined by staining with Evans Blue (EB) and Triphenyl tetrazolium chloride (TTC), respectively. EP94 reduced IS/AAR when administered as a double bolus (0.5µg/kg per dose), whereas single (1μg/kg) or triple boluses (0.5μg/kg per dose) did not confer any protection. Reduction of IS/AAR was of highest magnitude if EP94 was administered 5 and 0min before the 30min ischemic period (47% reduction, P<0.05), with declining cardioprotective effect with later administration during ischemia. When EP94 was administered after 15 and 20min of a 40-min ischemic period, reduction of IS/AAR was of the same magnitude as when given after 5 and 10min of a 30-min ischemic period. It is concluded that EP94 confers cardioprotection after double bolus administration. The effects are highly dependent on the timing of administration in relation to ischemia and reperfusion. Time of reperfusion from drug administration seems to be more critical than the total duration of ischemia.

Silent myocardial ischaemia in diabetic patients after general anaesthesia with 24 h intravenous opioids or with epidural analgesia

ObjectiveTo evaluate the effect of general anaesthesia with either continuous i.v. opioids (G/O) or thoracic epidural analgesia (G/EP) on postoperative transient myocardial ischaemia (TMI) in type 2 diabetic patients undergoing open cholecystectomy.MethodologyThis randomised controlled study was conducted on 50 patients with D.M. Patients were divided into G/O group or G/EP group. All patients had negative stress exercise test and at least two cardiac risks preoperatively. Epidural analgesia was established by 15 ml of ropivacaine 0.2% with fentanyl 2 μg/ml followed by 5–8 ml/h of ropivacaine 0.1% with fentanyl 1 μg for 24 h postoperatively. Both studied groups received same general anaesthesia. Continuous i.v. fentanyl 100 μg/h was given intraoperatively in group G/O followed by i.v. morphine PCA. Primary outcome measured postoperative TMI using 24 h continuous ST segment analysis, endothelin-1(ET-1), troponin T, creatine kinase MB (CK-MB), and CKMB/CK preoperatively, 8 h and 24 h postoperatively. Second outcome measured dynamic stress (perioperative heart rate, blood pressure and postoperative pain).ResultsEndothelin-1 was above cutoff level preoperatively and rose up dramatically postoperatively in both studied groups. G/EP attenuated ET-1 elevation than G/O. Troponin T and CK-MB did not rise postoperatively in both studied groups. Postoperative CK-MB/ CK ratio was higher than 10% in 12 and eight patients in group G/O and G/EP, respectively. Twelve cardiac ischaemic events were noticed in four patients in group G/O and four events in two patients in group G/EP without significant difference in total duration of ischaemia between groups. G/EP lowered HR more significantly intraoperatively and gave better pain control for 4 h postoperatively. In conclusion, D.M was associated with high ET-1 level. Upper abdominal surgery increased ET-1 release. G/EP attenuated ET-1 release more than G/O and produced more stable haemodynamic parameters and less postoperative pain. No superior cardioprotective effect was noticed in G/EP over G/O.

Giant focal nodular hyperplasia determining Budd–Chiari syndrome: an operative challenge requiring 210 min of liver ischemia

Focal nodular hyperplasia (FNH) is a relatively common benign liver tumor with rare indications to surgery. Early after pregnancy, a 35-year-old woman developed right upper quadrant abdominal pain with fever. A large abdominal mass was palpable. Abdominal CT scan showed a 18-cm FNH substituting all liver segments but S6 and S7, compressing middle and left hepatic vein near their origin, displacing and compressing right hepatic vein, with ascites. Surgery consisted of a left hepatectomy extended to S5-S8 and S1. Main technical challenge was the preservation of the right hepatic vein. Intermittent pedicle clamping was performed, associated with hepatic vascular exclusion with preservation of caval flow; total duration of ischemia was 210 min. The postoperative course was uneventful, except for a transient fall in prothrombin time, and the formation of a sub-diaphragmatic serous collection, which was percutaneously drained. The patient is well 25 months after the operation. To our knowledge, this is the second reported case requiring surgery for a FNH causing a Budd-Chiari syndrome. In these peculiar cases a cumbersome operation may be required, maximizing all precautions to perform a risk-free procedure.

Statin Therapy and the Elderly

In the United States, the prevalence of coronary and other cardiovascular diseases increases with age, reflecting in part the cumulative effect of lifetime exposure to cardiovascular risk factors.1 Coronary and cerebrovascular atherosclerosis in the elderly (≥65 years of age) is a growing clinical problem because of the population’s increasing longevity. Despite this evidence, cardiovascular risk in elderly patients is demonstrably undermanaged according to several epidemiological studies.2–4 In a Canadian study, paradoxically, elderly coronary patients who were at the highest risk for recurrent disease appeared to be the least likely to receive preventive treatment.4 Several factors may contribute to this poor level of management, such as confusion surrounding the relevance of certain modifiable risk factors to this age group, the cost-effectiveness of preventing coronary heart disease (CHD) in older patients, and concerns about the impact of therapies on safety and quality of life. Article p 700 Despite early studies that questioned the association of cholesterol with coronary risk in the elderly, the available epidemiology now favors the perspective that cholesterol remains an important modifiable risk factor in patients ≥65 years of age, especially after adjustment for the presence of comorbid conditions.5 Growing evidence demonstrates the benefit of treating higher-risk older patients. In this issue of Circulation , Deedwania et al6 present the results of the Study Assessing Goals in the Elderly (SAGE), which compares the effect of intensive (atorvastatin 80 mg/d) compared with moderate (pravastatin 40 mg/d) cholesterol lowering with statins in a cohort of 893 men and women 65 to 85 years of age with coronary artery disease. SAGE evaluated the absolute change in total duration of ischemia as measured by 48-hour Holter monitoring from baseline to 1 year. Although total ischemia duration was reduced significantly in both arms compared with baseline, the intensive strategy …

Effects of Intensive Versus Moderate Lipid-Lowering Therapy on Myocardial Ischemia in Older Patients With Coronary Heart Disease

Clinical trials have demonstrated that, compared with placebo, intensive statin therapy reduces ischemia in patients with acute coronary syndromes and in patients with stable coronary artery disease. However, no studies to date have assessed intensive versus moderate statin therapy in older patients with stable coronary syndromes. A total of 893 ambulatory coronary artery disease patients (30% women) 65 to 85 years of age with > or = 1 episode of myocardial ischemia that lasted > or = 3 minutes during 48-hour ambulatory ECG at screening were randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d and followed up for 12 months. The primary efficacy parameter (absolute change from baseline in total duration of ischemia at month 12) was significantly reduced in both groups at month 3 and month 12 (both P<0.001 for each treatment group) with no significant difference between the treatment groups. Atorvastatin-treated patients experienced greater low-density lipoprotein cholesterol reductions than did pravastatin-treated patients, a trend toward fewer major acute cardiovascular events (hazard ratio, 0.71; 95% confidence interval, 0.46, 1.09; P=0.114), and a significantly greater reduction in all-cause death (hazard ratio, 0.33; 95% confidence interval, 0.13, 0.83; P=0.014). Compared with moderate pravastatin therapy, intensive atorvastatin therapy was associated with reductions in cholesterol, major acute cardiovascular events, and death in addition to the reductions in ischemia observed with both therapies. The contrast between the therapies' differing efficacy for major acute cardiovascular events and death and their nonsignificant difference in efficacy for reduction of ischemia suggests that low-density lipoprotein cholesterol-lowering thresholds for ischemia and major acute cardiovascular events may differ. The Study Assessing Goals in the Elderly (SAGE) demonstrates that older men and women with coronary artery disease benefit from intensive statin therapy.

Factors associated with post-operative myocardial ischaemia in elderly patients undergoing major non-cardiac surgery

Forty patients (> 65 years) undergoing hip arthroplasty or peripheral vascular surgery both associated with high risk for post-operative myocardial ischaemia were randomized to receive either spinal or general anaesthesia. Ambulatory ECG recording (Holter) until the third post-operative morning, a daily 12-lead ECG and serum creatine kinase and troponine concentrations were obtained. The number of ischaemic episodes, total duration of ischaemia and ischaemic minutes per hour were noted for each patient perioperatively. Sixteen of the patients (40%) had post-operative myocardial ischaemia. An intra-operative increase in the plasma concentration of norepinephrine but not epinephrine was detected in the patients who later developed post-operative myocardial ischaemia. The increase in plasma norepinephrine concentrations correlated with the decrease in core temperature. The type of anaesthesia had no effect on the incidence of myocardial ischaemia during or after surgery. Our results suggests that intraoperatively decreased core temperature and the increase in plasma concentration of norepinephrine probably caused peripheral vasoconstriction leading to latent cardiac dysfunction. These events should be avoided in the patients at risk of post-operative cardiac ischaemia.

Comparison of the Effect of Two Metoprolol Formulations on Total Ischaemic Burden

Objective: To compare the effect of two sustained-release formulations of metoprolol — metoprolol succinate controlled-release formulation with zero-order kinetics (M CR/Zok) and metoprolol tartrate conventional sustained-release formulation (M ret.) — on total ischaemic burden in patients with stable angina pectoris. Patients and Methods: This randomised, double-blind, crossover study involved 52 patients with stable angina pectoris and at least six proven ST-segment depressions on 24-hour ambulatory ECG. After a 9-day placebo washout phase, patients were randomised to receive either M CR/Zok 95mg once daily for 4 weeks and then M ret. 200mg once daily for 4 weeks, or the same drugs in the reverse order. ST-segment parameters, cardiological and haemodynamic parameters were evaluated from 24-hour ambulatory ECG recordings. Results: M CR/Zok and M ret. significantly reduced the median number of ischaemic episodes per 24 hours from 19.15 with placebo to 2.07 with M CR/Zok and 3.74 with M ret. For placebo, M CR/Zok and M ret., the total duration of ischaemia was 39.12, 2.58 and 4.42 minutes, respectively, and the maximum episode duration was 7.5, 1.0 and 1.0 minutes, respectively. The maximum ST-segment depression was 1.65mm with placebo and 1.10mm with M CR/Zok and M ret. The number of angina attacks per 30 days was reduced compared with the placebo phase, from a median of 10.0 to 2.14 with M CR/Zok and 2.68 with M ret. Correspondingly, the number of units of short-acting nitrates consumed fell from 6.67 to 2.14 with M CR/Zok and 2.18 with M ret. M CR/Zok and M ret. lowered the average heart rate from 80.0 to 69.0 and 72.0 beats/min, respectively. All these decreases were significant relative to placebo (p < 0.001), but (with the exception of heart rate) there was no significant difference between M CR/Zok and M ret. for any parameter. 19 patients experienced adverse events with placebo, 24 with M CR/Zok and 30 with M ret. Conclusion: Our results show that M CR/Zok 95 mg/day or M ret. 200 mg/day taken once daily have similar efficacy on total ischaemic burden in patients with stable angina pectoris. M CR/Zok tends to be better tolerated.

Acute heavy alcohol intake increases silent myocardial ischaemia in patients with stable angina pectoris.

To evaluate the effect of acute alcohol ingestion on myocardial ischaemia in patients with coronary heart disease and stable angina. Randomised crossover study using fruit juice with and without ethanol. Division of cardiology in a university hospital. 20 patients with stable exertional angina and > or = 50% luminal diameter narrowing of at least one major coronary artery. Each patient was studied on two separate days, once after administration of 1.25 g of ethanol per kilogram of body weight diluted to 15% in juice, and once after an equivalent volume of juice; both tests were in the evening and lasted 90 minutes. The patients were scheduled to have 8 periods of walking for 10 min according to a time table. An ambulatory electrocardiogram and the occurrence of anginal attacks were recorded and blood pressure and blood ethanol concentration were measured until the next morning. The blood ethanol concentration (mean (SD)) rose to 28.8 mmol/l (1.3 (0.4)/1000). Alcohol raised the systolic blood pressure from 132 (16) to 141 (14) mm Hg (P < 0.05 compared with juice). The mean heart rate increased from 57 (7) to 64 (8) beats/min (P < 0.05) for 13 hours after ethanol ingestion compared with juice. The total duration of ischaemia during the ethanol test was 3.5 (median, range 0-80) min, compared with 0 (range 0-67) min for the juice test (P < 0.05). The difference resulted mainly from more silent ischaemia after ethanol ingestion (2.3 (0-80) v 0 (0-67) min; P < 0.05). The ST segment depression time integral increased during the ethanol test (4.4 (0-170) mm x min) relative to that during the juice test (0 (0-103) mm x min; P < 0.01) and especially during the following 13 hours after alcohol (3.5 (0-123) mm x min) compared with juice (0 (0-67) mm x min; P < 0.005). There were no changes in the number, duration, or ST segment depression time integral of the episodes of symptomatic angina, indicating that ethanol augmented the appearance of silent ischaemia. Acute heavy ethanol drinking aggravates myocardial ischaemia in patients with stable angina pectoris.

Ischemia-reperfusion increases gastric motility and endothelin-1-induced vasoconstriction.

The purpose of our study was to 1) examine the effect of ischemia-reperfusion on gastric vascular resistance and motility, 2) determine whether endothelin-1 (ET-1)-induced vasoconstriction is enhanced after ischemia-reperfusion, and 3) assess the effect of superoxide dismutase (SOD) on these ischemia-reperfusion-induced alterations. These experiments used a mechanically perfused ex vivo gastric segment of chloralose-anesthetized dogs. We first evaluated the effect of varying the duration of total ischemia on reperfusion-induced changes in gastric vascular resistance and motility. In other experiments, responses to ET-1 (10(-10) M) were compared before and after 30-min ischemia and 30-min reperfusion, with saline or SOD (10 U/ml) infused intra-arterially to the stomach during reperfusion. Our results show that 1) after ischemia, vasodilation is seen initially on reperfusion followed by a slowly developing, progressive increase in vascular resistance, 2) the force of gastric contractions was reduced during ischemia but elevated immediately on reperfusion, 3) vasoconstrictor responses to ET-1 are enhanced after ischemia-reperfusion, and 4) SOD reduced the enhanced response to ET-1 and force of contractions. Our findings support the hypothesis that reactive oxygen metabolites contribute to augmented vascular reactivity and hypercontractility after ischemia-reperfusion.

Trimetazidine European Multicenter Study versus propranolol in stable angina pectoris: Contribution of Holter electrocardiographic ambulatory monitoring

The major objective of the Trimetazidine European Multicenter Study (TEMS) was to compare in a double-blind trial the anti-ischemic effects of trimetazidine (20 mg 3 times daily) with those of propranolol (40 mg 3 times daily). The inclusion criteria were based on an abnormal response to a multistage exercise test. After 3 months of treatment the improvements noted in all exercise testing data were similar in the trimetazidine and propranolol groups; similar data were obtained for the grades and severity of anginal attacks during daily life (from patient diaries). A 24-hour Holter monitoring was performed at entry and at the end of the study, but an abnormal Holter monitoring (1 -mm ST-segment depression during at least 1 minute) was not an inclusion criterion. This explains why at entry only 50% of the patients in both groups had an abnormal Holter recording. After 3 months of treatment, there were no significant differences between the 2 groups, but we observed a trend toward a decrease in ambulatory ischemia in the trimetazidine group and a trend toward an increase in ambulatory ischemia in the propranolol group. These data in the propranolol group are in total disagreement with the available literature on β blockers, which was due to a totally erratic behavior pattern in 2 patients in the propranolol group. When we excluded these 2 erratic cases from the propranolol group and extended our analysis to all available paired comparisons (day — 14 to day 30 and day 0 to day 90), we were able to compare 44 and 60 observations, both off therapy and on either propranolol or trimetazidine, respectively. The number of ischemic episodes was significantly reduced with trimetazidine (p <0.02) but not with propranolol. The total duration of ischemia was reduced (but not significantly) in the trimetazidine group; surprisingly, this reduction was essentially due to a reduction in symptomatic ischemic episodes. A circadian ischemic profile was noted in both groups, but it was notably more reduced in the trimetazidine group; surprisingly, this reduction was also essentially due to a reduction in symptomatic ischemic episodes. We conclude from these data that, (1) to draw conclusions on ischemic Holter monitoring data, an abnormal ischemic Holter should be one of the criteria to enter the study; (2) a 48-hour ambulatory recording is likely to provide more reliable information; and (3) much larger groups should be studied to avoid statistical interference from erratic cases. The major objective of the Trimetazidine European Multicenter Study (TEMS) was to compare in a double-blind trial the anti-ischemic effects of trimetazidine (20 mg 3 times daily) with those of propranolol (40 mg 3 times daily). The inclusion criteria were based on an abnormal response to a multistage exercise test. After 3 months of treatment the improvements noted in all exercise testing data were similar in the trimetazidine and propranolol groups; similar data were obtained for the grades and severity of anginal attacks during daily life (from patient diaries). A 24-hour Holter monitoring was performed at entry and at the end of the study, but an abnormal Holter monitoring (1 -mm ST-segment depression during at least 1 minute) was not an inclusion criterion. This explains why at entry only 50% of the patients in both groups had an abnormal Holter recording. After 3 months of treatment, there were no significant differences between the 2 groups, but we observed a trend toward a decrease in ambulatory ischemia in the trimetazidine group and a trend toward an increase in ambulatory ischemia in the propranolol group. These data in the propranolol group are in total disagreement with the available literature on β blockers, which was due to a totally erratic behavior pattern in 2 patients in the propranolol group. When we excluded these 2 erratic cases from the propranolol group and extended our analysis to all available paired comparisons (day — 14 to day 30 and day 0 to day 90), we were able to compare 44 and 60 observations, both off therapy and on either propranolol or trimetazidine, respectively. The number of ischemic episodes was significantly reduced with trimetazidine (p <0.02) but not with propranolol. The total duration of ischemia was reduced (but not significantly) in the trimetazidine group; surprisingly, this reduction was essentially due to a reduction in symptomatic ischemic episodes. A circadian ischemic profile was noted in both groups, but it was notably more reduced in the trimetazidine group; surprisingly, this reduction was also essentially due to a reduction in symptomatic ischemic episodes. We conclude from these data that, (1) to draw conclusions on ischemic Holter monitoring data, an abnormal ischemic Holter should be one of the criteria to enter the study; (2) a 48-hour ambulatory recording is likely to provide more reliable information; and (3) much larger groups should be studied to avoid statistical interference from erratic cases.

Myocardial uptake of indium-111 antimyosin after coronary angioplasty. Relationship with the total burden of ischaemia.

Indium-111 antimyosin scintigraphy was performed in 24 consecutive patients after percutaneous transluminal coronary angioplasty to assess whether repeated periods of ischaemia during balloon inflation results in myocardial cell damage even after a successful procedure. Patients with unstable angina, prior myocardial infarction and whose procedure was complicated were excluded. Indium-111 monoclonal antimyosin antibodies (80 MBq) were injected 24 h after coronary angioplasty and planar images were collected 24 h later. The relative antimyosin uptake was assessed subjectively and by a heart/lung count density ratio. In addition, the intracardiac gradient of activity was assessed by a count density profile analysis of the cardiac region of interest to distinguish better the focal as opposed to the diffuse antimyosin uptake. The antimyosin uptake index was calculated by multiplying the heart/lung ratio to the intracardiac gradient of activity. After coronary angioplasty, nine patients had minor ST-T wave changes on the surface ECG, but no patient demonstrated a new Q wave. Only three patients showed a mild rise in cardiac enzyme (CK-MB) serum levels. Indium-111 antimyosin uptake (heart/lung > 1.55) was present in eight patients (33%) and was intense (heart/lung > 1.9) in five (21%). Antimyosin uptake was always seen in myocardial segments corresponding to the treated coronary artery. Patients with a positive antimyosin scan had a longer duration of balloon-induced ischaemia compared with patients with no evidence of antimyosin uptake (541 +/- 211 vs 331 +/- 137 s, P < 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Medical treatment to reduce total ischemic burden: Total ischemic burden bisoprolol study (TIBBS), a multicenter trial comparing bisoprolol and nifedipine

Objectives. We compared the effects of bisoprolol on transient myocardial ischemia with those of nifedipine in patients with chronic stable angina.Background. Both beta-adrenergic blocking agents and calcium antagonists reduce transient ischemic episodes, but comparisons of these agents have been made in only a few larger studies.Methods. The Total Ischemic Burden Bisoprolol Study (TIBBS) was a randomized double-blind controlled study with two parallel groups; 330 patients from 30 centers in seven European countries with stable angina pectoris, a positive exercise test and more than two transient ischemic episodes during 48 h of Holter monitoring (central evaluation) were included. Of these patients 161 were randomized to receive bisoprolol and 169 to receive nifedipine slow release. There were two treatment phases of 4 weeks each, with 48-h Holter monitoring after each phase. During phase 1, patients received either 10 mg of bisoprolol daily or 2 × 20 mg of nifedipine slow release. During phase 2, they received either 20 mg of bisoprolol daily or 2 × 40 mg of nifedipine slow release.Results. In phase 1 of the trial, 4 weeks of bisoprolol therapy (10 mg daily) reduced the mean [±SD] number of transient ischemic episodes from 8.1 ± 0.6 to 3.2 ± 0.4/48 h. Nifedipine (2 × 20 mg) reduced transient ischemic episodes from 8.3 ± 0.5 to 5.9 ± 0.4/48 h. Total duration of ischemia was reduced from 99.3 ± 10.1 to 31.9 ± 5.5 min/48 h with bisoprolol and from 101 ± 9.1 to 72.6 ± 8.1 min/48 h with nifedipine. Reductions were statistically significant for both drugs; the difference between bisoprolol and nifedipine was also significant (p < 0.0001). Bisoprolol reduced the heart rate at onset of episodes by 13.7 ± 1.4 beats/min from a baseline value of 99.5 ± 1.2 beats/min (p < 0.001). Heart rate was unchanged with nifedipine. Bisoprolol had significantly higher responder rates than nifedipine. Doubling of the dose in phase 2 of the trial had small additive effects. Only bisoprolol showed a marked circadian effect by reducing the morning peak of transient ischemic episodes (by 68% at peak time, 8:00 to 8:59 am).Conclusions. Both bisoprolol and nifedipine reduced the number and duration of transient ischemic episodes in patients with chronic stable angina. Bisoprolol was significantly more effective than nifedipine in both doses tested and reduced the morning peak of ischemic activity.

Induction of silent myocardial ischemia with mental stress testing: Relation to the triggers of ischemia during daily life activities to ischemic functional severity

Objectives. This study examined the relations among the triggers of ischemia during the activities of daily life, mental stress-induced ischemia in the laboratory and functional severity of ischemia on exercise testing.Background. Myocardial ischemia is readily induced with exercise testing, but most episodes of ischemia in daily life occur during relatively sedentary activities. Although mental and emotional arousal are known to trigger myocardial ischemia, mental stress testing induces ischemia in only ~ 50% of patients with active coronary disease. It is not known whether such patients are particularly susceptible to nonexertional ischemia during daily activity.Methods. We studied 45 men (mean age ± SD 58 ± 9 years) with coronary artery disease by means of 48-h Holter ambulatory electrocardiography for ST segment analysis and quantification of physical and mental activity with a structured diary system. These data were cross-tabulated with new left ventricular dyssynchrony (detected on two-dimensional echocardiography) induced by two mental stressors and by bicycle exercise.Results. During mental stress testing, 24 patients (53%) (Group I) had a new wall motion abnormality: the other 21 patients (Group II) did not. The average wall motion dyssynchrony score increased from 1.20 ± 0.29 to 1.34 ± 0.36 (p = 0.001), but the increase was less than that with exercise stress (1.52 ± 0.41, p = 0.001). The total duration of ischemia during sedentary activities was greater in Group I (22.9 ± 24.5 min) than in Group II (3.6 ± 3.9 min, p = 0.025). Group I had more ischemic events while sedentary (23 of 290 diary entries) than did Group II (8 of 256 diary entries, p = 0.015). The magnitude of dyssynchrony with mental stress and the number of mental stressors capable of triggering ischemia were related to severity of ischemia with exercise.Conclusions. Patients with ischemia during mental stress testing also have increased ischemia during sedentary activities in daily life. This finding may reflect greater functional severity of coronary artery disease or a propensity toward coronary vasoconstriction while sedentary.

Effect of coronary reocclusion after initial reperfusion on ventricular function and infarct size

Reocclusion of a coronary artery after thrombolytic therapy occurs in approximately 12% to 33% of patients; however, there are few experimental data concerning reocclusion. Accordingly, to compare the effects of reocclusion versus sustained occlusion on the myocardium, a canine model (n = 12) of 2 h of left circumflex artery occlusion, 1 h of reperfusion and 1 h of reocclusion was studied. In a control group (n = 11), 3 h of circumflex artery occlusion was followed by 1 h of reperfusion. As a result, both groups had the same total duration of ischemia (3 h) and reperfusion (1 h). Hemodynamic measurements, radioactive microsphere injections and two-dimensional echocardiography were performed at baseline, occlusion and reperfusion for both groups and at the end of reocclusion for the experimental group. In vivo risk area was determined with Evans blue dye and infarct size with triphenyltetrazolium staining methods.Similar decreases in myocardial blood flow after coronary occlusion and similar reperfusion blood flows occurred in both groups. Despite intervening reperfusion in the reocclusion group, no significant difference was found in the infarct size/risk area ratio between the reocclusion and control groups (54.5 ± 6.9% vs. 48.4 ± 5.1%, respectively, p = NS). Two-dimensional echocardiography demonstrated a similar degree and extent (159 ± 9 ° vs. 153 ± 12 °, p = NS) of left ventricular dysfunction with both the occlusion and reocclusion. In addition, there were no significant differences in global or regional left ventricular function between the two groups. However, reocclusion after reperfusion did produce a further deterioration in ischemic zone wall thickening (9.5 ± 2.0% to 0.7 ± 1.8%, p < 0.001).It is concluded that coronary reocdusion after initial reperfusion contributes to additional ischemic damage, so that the beneficial salvaging effects of reperfusion are negated. Furthermore, coronary reocdusion results in further ischemic dysfunction in the reperfused but hypokinetic myocardium.

Thrombolytic therapy in refractory unstable angina: The role of holter monitoring

We tested the safety and the usefulness of intravenous urokinase (2 million units administered over 30 min) in 44 patients with refractory unstable angina, defined as persistence of ischemic episodes during 48-h Holter monitoring (Phase 1) despite maximal medical therapy. After thrombolysis, recurrence of ischemia was observed during a week of observation in the CCU, including two 24-h Holter monitorings at the beginning and the end of the week (Phase 2). Seventeen patients completed the observation period without either symptomatic or asymptomatic ischemic episodes (Group A); the remaining 27 continued to manifest ischemia (Group B). No bleeding complications occurred. Within a 6-month follow-up, 2 patients of Group A had recurrence of unstable angina while in Group B, 19 patients had refractory angina or a major cardiac event [10 patients underwent coronary artery bypass surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA) for refractory angina (p less than 0.001), 6 other patients with refractory angina continued medical therapy, one patient had a myocardial infarction, and two patients died]. In Phase 1 the duration of total ischemia (min/24 h) was a relevant prognostic marker: higher duration correlated with adverse clinical outcome (p less than 0.01). In comparison to Phase 1, duration of total ischemia in Phase 2 was significantly reduced in both groups (16.9 +/- 19.6 vs. 25.4 +/- 17.7; p less than .001). A percent value expressing this variation was calculated for each patient: the variation thus obtained again gave information on the clinical outcome--the greater the reduction, the lower the risk of cardiac events (p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Perioperative myocardial ischemia in patients undergoing noncardiac surgery—II: Incidence and severity during the 1st week after surgery

Because of the importance of postoperative myocardial ischemia and because substantial physiologic changes can occur for prolonged periods postoperatively, the incidence, severity and temporal course of myocardial ischemia were studied in 100 high risk patients during the 1st week after major noncardiac surgery. Electrocardiographic (ECG) changea consistent with ischemia were continuously monitored using ambulatory solid state ECG in the 100 patients with or at risk for coronary artery disease. Ischemic episodes were defined as reversible ST segment depression ≥1 mm or elevation ≥2 mm above the baseline value, with the baseline adjusted for respiratory and positional variation and temporal drift. All ischemic episodes were confirmed by three independent blinded investigators using hard-copy recordings. Total ECG monitoring time was 10,445 h.Twenty-seven patients (27%) developed 437 episodes of ischemia during the 1st week after surgery. The total duration of ischemia was 18,658 min, or 1.8 min of ischemia/h monitored. Ischemia was most severe during the early (days 0 to 3) versus late (days 4 to 7) postoperative period: 284 versus 153 episodes; 2.2 versus 1.2 min of ischemia/h. The greatest severity occurred on postoperative day 3: 109, episodes, 3.4 min of ischemia/h monitored, 1.5 mm mean ST change and 130 min mean duration. However, in 8% of patients, severe episodes also occurred late: postoperative day 6 = 44 episodes, 1.7 min of ischemia/h monitored, 1.3 mm mean ST change (59% ≥ 2 mm) and 92 min mean duration. Most ischemic episodes (57%) were associated with tachycardia. Eighty-four percent of episodes were silent, unaccompanied by symptoms of angina, pulmonary congestion or syncope. All five severe adverse cardiac outcomes (unstable angina, myocardial infarction or cardiac death) were preceded by postoperative ischemia occurring ≥1 day before the outcome.It is concluded that in at-risk patients undergoing noncardiac surgery; 1) postoperative ECG ST changes consistent with myocardial ischemia are most common during the 1st 3 days after surgery, with changes persisting for ≥1 week; 2) postoperative ischemia is clinically silent throughout the entire period and therefore difficult to detect; 3) postoperative ischemia may be related to the persistently elevated heart rate during the 1st week after surgery; and 4) an association between both early and late postoperative ischemia and severe cardiac outcomes is suggested.

Effect of nifedipine on total ischemic activity and circadian distribution of myocardial ischemic episodes in angina pectoris

A randomized, double-blind, crossover study was conducted in 10 patients to assess the effect of nifedipine versus placebo on total ischemic activity and circadian distribution of ischemic episodes. After baseline exercise treadmill testing and 48-hour ambulatory electrocardiographic ST-segment monitoring, patients received either nifedipine (mean dose, 80 mg/day) or placebo administered 4 times per day, with the initial dose taken immediately upon arising in the morning. Patients were maintained on a stable dose of each study drug for 7 days, after which they underwent repeat exercise treadmill testing and 48-hour ambulatory electrocardiography. During exercise treadmill testing, greater exercise duration was achieved by patients receiving nifedipine than by those receiving placebo (421 ± 121 vs 353 ± 155 seconds, respectively; p < 0.05). Time to ⩾1 mm ST depression was significantly greater with nifedipine (282 ± 146 seconds) than at baseline (130 ± 72 seconds, p < 0.003) and with placebo (150 ± 98 seconds, p < 0.0005). During ambulatory electrocardiographic monitoring, nifedipine reduced both the total number of ischemic episodes (18 vs 54 at baseline and 63 with placebo; p < 0.02 for both) and the total duration of ischemia (260 vs 874 at baseline and 927 minutes with placebo; p < 0.02 for both). The surge of ischemia between 06:00 and 12:00 noted at baseline and during placebo therapy was nearly abolished during nifedipine treatment. Nifedipine at this dosage, administered in this manner, is effective in reducing total ischemic activity and may prevent morning surges of ischemic episodes.