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BACKGROUND: Acute kidney injury (AKI) is a well-recognised complication of cardiac catheterisation and percutaneous coronary intervention (PCI). However, the incidence of chronic kidney disease (CKD) after catheterisation and PCI has not been fully evaluated. A number of risk factors have been implicated in the development of AKI following cardiac catheterisation. Transradial access could lead to a lower incidence of CKD after catheterisation or PCI because of less catheter contact with aortic atheroma, and reduced potential for atheroembolism. OBJECTIVE: To determine the incidence of CKD onset and its association with arterial access in patients after cardiac catheterisation or PCI. METHODS AND RESULTS: Linkages between the British Columbia (BC) Cardiac Registry (N=69 214) patients who underwent catheterisation or PCI between 1999 and 2005 and the BC Renal Database were determined. Within 6 months after the cardiac procedure 0.4% of patients developed dialysis dependency, 0.2% in the transradial versus 0.4% in the transfemoral group (p<0.0001); 0.3% of patients developed stage 4 or 5 CKD, 0.1% in the transradial versus 0.4% in the transfemoral group (p<0.0001); 0.9% of patients developed new CKD, 0.2% in the transradial versus 1.2% in the transfemoral group (p<0.0001). After adjusting for baseline characteristics the femoral access site had an OR of 4.36 (95% CI 2.48 to 7.66) for the development of the composite end point of new dialysis, new stage 4 or 5 CKD or new CKD. CONCLUSIONS: In this large database of current practice coronary catheterisation and PCI, the incidence of CKD onset within 6 months of the procedure was 0.9%. The transradial access site is associated with less CKD than the femoral approach. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bleeding and transfusion after percutaneous coronary intervention (PCI) are known predictors of mortality. Transradial arterial access reduces bleeding and transfusion related to femoral access complications, although its association with mortality is unknown. OBJECTIVE: To determine the association of arterial access site (radial or femoral) with transfusion and mortality in unselected PCIs. DESIGN, SETTING AND PATIENTS: By data linkage of three prospectively collated provincial registries, 38,872 procedures in 32,822 patients in British Columbia were analysed. The association between access site, transfusion and outcomes was assessed by logistic regression, propensity score matching and probit regression. MAIN OUTCOME MEASURES: 30-Day and 1-year mortality. RESULTS: 1134 (3.5%) patients had at least one blood transfusion. Transfused patients had a significantly increased 30-day and 1-year mortality, adjusted odds ratio (95% CI) 4.01 (3.08 to 5.22) and 3.58 (2.94 to 4.36), respectively. By probit regression the absolute increase in risk of death at 1 year associated with receiving a transfusion was 6.78%. The number needed to treat was 14.74 (prevention of 15 transfusions required to 'avoid' one death). Radial access halved the transfusion rate. After adjustment for all variables, radial access was associated with a significant reduction in 30-day and 1-year mortality, odds ratio = 0.71 (95% CI 0.61 to 0.82) and 0.83 (0.71 to 0.98), respectively (all p<0.001). CONCLUSIONS: In a registry of all comers to PCI, transradial access was associated with a halving of the transfusion rate and a reduction in 30-day and 1-year mortality. [ABSTRACT FROM AUTHOR]

Background: Guidelines recommend clopidogrel use for 6-12 months following drug-eluting stent (DES) implantation and 1-12 months following bare metal stent (BMS) implantation. The role of clopidogrel beyond 12 months is unclear., Methods: We linked hospital administrative, community pharmacy and cardiac revascularization data to determine clopidogrel use and outcomes for all patients (those with acute presentations and those with stable angina) receiving a coronary stent in British Columbia 2004-2006, with follow-up until the end of 2008. Cox proportional hazard regression was performed to evaluate the effect of clopidogrel duration (≤12 vs. >12 months) on outcomes following BMS or DES implantation. Patients who died ≤12 months from index stent placement were excluded., Results: A total of 15,629 patients were included in the study. Of 3599 patients who received at least one DES and 12,030 patients who received only BMS, 1326 (37 %) and 2121 (18 %), respectively, filled a prescription for clopidogrel >12 months from the index procedure. The mean duration of clopidogrel was 406 ± 35 days and 407 ± 37 days in the prolonged use (>12 months) DES and BMS cohorts, respectively, compared with 224 ± 112 days (p < 0.001) and 122 ± 117 days (p < 0.001), respectively, for patients receiving clopidogrel ≤12 months. Clopidogrel use beyond 12 months was associated with a reduction in mortality [hazard ratio (HR) 0.66, 95 % confidence interval (CI) 0.45-0.97] and the composite of mortality and readmission for myocardial infarction (HR 0.72, 95 % CI 0.55-0.94) in patients treated with DES, but not BMS alone. Prolonged clopidogrel use was not associated with bleeding-related mortality., Conclusions: Clopidogrel use beyond 12 months was associated with a reduction in death and hospitalization for myocardial infarction following DES, but not BMS, implantation. Our findings support a longer duration of clopidogrel therapy for patients treated with DES.

Background: Patients frequently experience difficulties with medication compliance after hospital discharge. We investigated the effect of a delay in filling a first clopidogrel prescription after hospital discharge on clinical outcomes subsequent to coronary stenting., Methods and Results: Hospital administrative, community pharmacy, and cardiac revascularization data were determined for all patients receiving a coronary stent in British Columbia 2004-2006 with follow-up out to 2 years. Cox's proportional hazard regression analysis, adjusting for baseline demographics and procedural variables, was performed to examine the effects of delay in filling a clopidogrel prescription after hospital discharge on clinical outcomes.Of 15 629 patients treated with coronary stents, 3599 received at least 1 drug-eluting stent (DES), whereas 12 030 received bare metal stents (BMS) alone. In total, 1064 (30%) and 3758 (31%) patients in the DES and BMS groups, respectively, failed to fill a prescription within 3 days of discharge (median, 1 day; interquartile range [IQR], 1 to 3). After regression analysis, a delay of >3 days was predictive of mortality and recurrent myocardial infarction (MI) irrespective of stent type (DES: hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.7 to 3.4; and HR, 2.0; 95% CI, 1.5 to 2.7, respectively, and BMS: HR, 2.2; 95% CI, 1.9 to 2.6; and HR, 1.8; 95% CI, 1.5 to 2.1, respectively). This excess hazard was greatest in the 30-day period immediately after hospital discharge (mortality: HR, 5.5; 95% CI, 3.5 to 8.6; and MI: HR, 3.1; 95% CI, 2.4 to 4.0, for all patients)., Conclusions: Delays in patients filling their first prescription for clopidogrel after coronary stenting are common and associated with adverse clinical outcomes, irrespective of stent type. Strategies to reduce delays have the potential to improve clinical outcomes., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Little is known about how corals sense and respond to light. In this report the proteome of coral is explored using 2D protein electrophoresis in two species, Montastraea cavernosa and Acropora millepora. Multiple protein species have major shifts in abundance in both species when sampled in daylight compared to corals sampled late in the night. These changes were observed both in larvae lacking zooxanthellae and in adult tissue containing zooxanthellae, including both Pacific and Caribbean corals. When larvae kept in the dark were treated with either thapsigargin or ionomycin, compounds that raise the level of cytoplasmic calcium, the night pattern of proteins shifted to the day pattern. This implies that photoreceptors responding to light elevate calcium levels and that calcium acts as the second messenger relaying light responses in corals. Corals spawn at night, and spawning can be delayed by exposure to light or pushed forward by early artificial sunsets. In a series of behavioral experiments, treatment of corals with ionomycin or thapsigargin was found to delay broadcast spawning in M. franksi, demonstrating that pharmacologically altering cytoplasmic calcium levels generates the same response as light exposure. Together these results show that the photo-responsive cells of corals detect and respond to light by altering cytoplasmic calcium levels, similarly to the transduction pathways in complex invertebrate eyes. The primacy of cytoplasmic calcium levels in light responsivity has broad implications for coral reproduction, including predicting how different species spawn at different times after sunset and how reproductive isolation is achieved during coral speciation.

Background: Bleeding following percutaneous coronary intervention (PCI) is common and may lead to transfusion and death. Although previous work has examined the effect of red blood cell (RBC) transfusion in patients with coronary disease, no study had investigated whether transfusion of non-RBC components was associated with mortality following PCI., Methods: All subjects transfused in the 10 days following PCI were identified using the British Columbia Cardiac and Central Transfusion Registries. Patients undergoing cardiac surgery following PCI were excluded as transfusion was assumed to be due to surgical related bleeding. Transfusion products were categorised as RBC and non-RBC comprising platelets, plasma and cryoprecipitate. Blood product use was compared according to thirty day mortality using multivariate regression and propensity adjustment for confounding variables., Results: From a total of 32,580 patients who underwent PCI, 952 patients received at least 1 blood product within 10 days of PCI. Non-RBC transfusion occurred more commonly in the cohort of transfused patients dying within 30 days (p<0.001). After adjustment for baseline risk, transfusion of plasma/cryoprecipitate (HR 5.17; 95% C.I. 2.87-9.32, p<0.001) and platelets (HR 2.13; 95% C.I. 1.10-4.13, p=0.03) was associated with increased 30 day mortality. In a propensity risk adjusted model, transfusion of plasma/cryoprecipitate and RBC transfusion volume remained as significant predictors of 30-day mortality (p<0.001)., Conclusions: Transfusion following PCI appears to be associated with an increased risk of death within 30 days. We now report that transfusion with plasma rich non-RBC products may confer an additional mortality risk to patients undergoing PCI., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Coronary artery bypass grafting (CABG) performed within 5 days of clopidogrel administration is associated with increased bleeding. The impact of clopidogrel loading dose is unknown. We examined the effect of clopidogrel loading dose on bleeding outcomes in patients undergoing urgent CABG., Methods: Clinical outcomes were examined retrospectively for 196 consecutive patients undergoing urgent CABG within 5 days of a clopidogrel loading dose between January 2003 and June 2009. Major bleeding was defined as a fall in hemoglobin > 5 g/dL, fatal or intracranial bleeding, or cardiac tamponade., Results: One hundred forty-eight patients received 300 mg and 48 patients received ≥ 600 mg clopidogrel loading. Patients were predominantly male (78%) with a mean age of 66 ± 10 years. Mean duration from clopidogrel loading to CABG was 3.0 ± 1.5 and 3.0 ± 1.6 days for the 300 and 600 mg loading doses, respectively. Major bleeding occurred in 47% of patients receiving 300 mg and 73% of patients receiving ≥ 600 mg clopidogrel loading (P = .002). Compared with 300 mg, patients receiving ≥ 600 mg had greater 24-hour chest tube output (391 ± 251 vs 536 ± 354 mL, P = .01), stayed longer in surgical intensive care (4.3 ± 4.1 vs 5.0 ± 3.1 days, P = .0001), and trended toward greater reoperation for bleeding (5% vs 12%, P = .09). Following multivariate analysis, clopidogrel loading dose ≥ 600 mg (odds ratio 2.8, CI 1.2-6.6), preoperative hemoglobin (3.4, 2.7-5.0 per 1 g/dL increase), and female gender (2.9, 1.1-7.4) predicted major bleeding., Conclusions: Higher clopidogrel loading doses are associated with increased bleeding when administered within 5 days of CABG. The development of shorter-acting, reversible, oral antiplatelet agents may reduce perioperative bleeding in this population., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Blood transfusion has been associated with an increased mortality in patients undergoing percutaneous coronary intervention (PCI). Although the reasons for this remain unclear, it may be related to the structural and functional changes occurring within red blood cells (RBCs) during storage. We investigated whether RBC storage duration was associated with mortality in patients requiring transfusion after PCI., Methods: We collected data on all RBC transfusions occurring within 10 days of PCI (excluding those related to cardiac surgery) using the British Columbia Cardiac Registry and Central Transfusion Registry. Transfusion details were analyzed according to 30-day survival., Results: From a total of 32,580 patients undergoing PCI, 909 (2.8%) patients received RBCs with a mean storage duration of 25 +/- 10 days. In these 909 patients, mean transfusion volumes were lower in survivors (2.8 +/- 2.1 vs 3.8 +/- 2.9 U, P = .002) than those who died within 30 days. In a multivariate analysis to adjust for baseline risk, mean RBC storage age (HR 1.02 [95% CI 1.01-1.04], P = .002) and transfusion volume (HR 1.26 [95% CI 1.18-1.34], P < .001) both predicted 30-day mortality. Transfused patients who received only older blood (RBC min age >28 days) appeared to be at greater risk of death (HR 2.49 [95% CI 1.45-4.25], P = .001)., Conclusion: Red blood cell transfusion is associated with increased 30-day mortality in patients undergoing PCI. Although current transfusion practice permits RBC storage for up to 42 days, the use of older red cells may pose an additional hazard to this patient group., (2010 Mosby, Inc. All rights reserved.)

The demonstration that angiogenic growth factors can stimulate new blood vessel growth and restore perfusion in animal models of myocardial ischemia has led to the development of strategies designed for the local production of angiogenic growth factors in patients who are not candidates for conventional revascularization. The results of recent clinical trials of proangiogenesis gene therapy have been disappointing; however, significant limitations in experimental design, in particular in gene transfer strategies, preclude drawing definitive conclusions. In the REVASC study cardiac gene transfer was optimized by direct intramyocardial delivery of a replication-deficient adenovirus-containing vascular endothelial growth factor (AdVEGF121, 4 x 10(10) particle units (p.u.)). Sixty-seven patients with severe angina due to coronary artery disease and no conventional options for revascularization were randomized to AdVEGF121 gene transfer via mini-thoracotomy or continuation of maximal medical treatment. Exercise time to 1 mm ST-segment depression, the predefined primary end-point analysis, was significantly increased in the AdVEGF121 group compared to control at 26 weeks (P=0.026), but not at 12 weeks. As well, total exercise duration and time to moderate angina at weeks 12 and 26, and in angina symptoms as measured by the Canadian Cardiovascular Society Angina Class and Seattle Angina Questionnaire were all improved by VEGF gene transfer (all P-values at 12 and 26 weeks < or =0.001). However, if anything the results of nuclear perfusion imaging favored the control group, although the AdVEGF121 group achieved higher workloads. Overall there was no significant difference in adverse events between the two groups, despite the fact that procedure-related events were seen only in the thoracotomy group. Therefore, administration of AdVEGF121 by direct intramyocardial injections resulted in objective improvement in exercise-induced ischemia in patients with refractory ischemic heart disease.

There is limited data on patient preference for same-day discharge PCI. We contacted 953 patients who had same-day discharge radial PCI between 1998 and 2001 and checked whether they were satisfied with same-day discharge and whether they had any complications within 30 days post-PCI (vascular, repeat angiogram/PCI). Complications and health status were also verified by checking hospital records, our province-wide cath lab database and provincial vital statistics, as well as by contacting the referring doctor. A total of 811 patients responded. Of this total, 88.6% of the patients were satisfied with same-day discharge PCI, and 11.4% were not. Patients were significantly more satisfied with same-day discharge when they did not experience vascular complications (83.4% versus 91.5% satisfied with and without vascular complications at 24 hours, and 74.3% versus 90.9% at 30 days, p < 0.01). Patient preference on same-day discharge was the same regardless of whether they needed a repeat PCI within 30 days (p > 0.05). Patients for whom early discharge was important were significantly more satisfied with same-day discharge (97.9% versus 79.7% when early discharge was not important, p < 0.01). Patients who were reluctant to be discharged on the same day of the procedure were significantly less satisfied compared to those who were not (71.9% vs. 96.4% respectively, p < 0.01). A few patients (8.6%) had difficulty finding transportation home and were significantly less satisfied (70.0% vs. 90.3% when they found transportation easily, p < 0.01). In conclusion, same-day discharge is preferred by the majority of the patients undergoing radial PCI.

Transradial percutaneous coronary intervention (PCI) is a safe and effective method of percutaneous revascularization. However, there are no data on the efficacy of the transradial approach in left main (LM) PCI. We studied 80 patients (pts) who underwent LM PCI between February 1994 and January 2002, and compared the radial (27 pts) and femoral (53 pts) approaches. Patients were considered free of restenosis if they were free of angina and had a negative treadmill or nuclear imaging study 6 months post-PCI. Mean follow-up time was 27.4+/-23.0 months. Reason for PCI (stable angina, unstable angina, acute myocardial infarction) and lesion location (ostial, mid, distal) were similar in both groups (p>0.05), whereas mean ejection fraction was higher in the radial group (56.5+/-11.1% versus 49.2+/-14.7%, respectively; p<0.05). Sheath size (7 or 8 French; 44.4% radial versus 77.3% femoral) and amount of heparin used (9,192+/-3,645 IU versus 11,468+/-5,083 IU) were significantly larger in the femoral group (p<0.05), and the use of intra-aortic balloon pump was significantly more frequent (3.7% versus 22.6%). Mean fluoroscopy time (21.3+/-12.8 minutes versus 16.7+/-8.5 minutes), amount of contrast used (227+/-92 ml versus 225+/-85 ml), mean procedural time (67.0+/-27.6 minutes versus 73.4+/-32.7 minutes), procedure success (96.3% versus 98.1%), in-hospital major adverse cardiac events (MACE; 7.4% versus 5.6%) and 6-month MACE (14.8% versus 25.5%) were similar in the 2 groups (p>0.05). However, major vascular complications occurred only in the femoral group (5.7%). Radial LM PCI is as fast and successful as the femoral approach and results in fewer vascular complications.

Background: Excimer laser coronary angioplasty (ELCA) has not been used in the setting of highly calcified, tight stenoses because the energies required to use existing catheters would lead to excessive heat damage and dissection. There are, however, cases that frequently benefit from debulking prior to percutaneous intervention. A new, small laser catheter capable of high energies and repetition was previously examined in vitro. This study describes the first in vivo use., Purpose: To determine the safety and feasibility of a new, low profile, high energy laser catheter for creating a pilot hole to facilitate coronary angioplasty and stenting in patients with heavily calcified and occluded coronary arteries where a balloon has either failed to pass or was predicted to perform poorly. These patients represent the first patients treated with this new catheter., Methods: At a high volume center, seven consecutive patients with anatomy as summarized above were treated and studied with QCA and then followed for 30 days postprocedure for complications and Canadian Cardiovascular Society (CCS) angina class., Results: The laser catheter crossed five out of seven lesions and partially penetrated the remaining lesions. The mean maximum luminal diameter (MLD) postlasing was 1.0 mm with Thrombolysis in Myocardial Infarction (TIMI) 3 flow. It was possible to easily balloon and stent after the pilot hole creation in all but one patient. TIMI 3 was achieved for the final result after adjunct therapy in all patients. All patients except one, who died at 3 months postprocedure of stroke, were improved by an average of two angina classes. No late procedural-related complications developed., Conclusions: The new, low profile laser catheter is easy to use and achieved good results in cases where a balloon either failed to pass or was predicted to give poor results. Further trials are warranted for this niche technology.

Background: The introduction and refinement of coronary-artery stenting dramatically changed the practice of percutaneous coronary revascularization in the mid-1990s. We analyzed one-year follow-up data for all percutaneous coronary interventions performed in a large, unselected population in Canada to determine whether the use of coronary stenting has been associated with improved outcomes., Methods: Prospectively collected data on all percutaneous coronary interventions performed on residents of British Columbia, Canada, between April 1994 and June 1997 were linked to province-wide health care data bases to provide the date of the following end points: subsequent target-vessel revascularization, myocardial infarction, and death. Baseline characteristics and procedural variables were identified and Kaplan-Meier survival curves were generated for 9594 procedures divided into seven groups, one for each sequential half-year period., Results: The overall burden of coexisting illnesses remained stable throughout the study period. A large increase in the rate of coronary stenting (from 14.2 percent in the period from April to June 1994 to 58.7 percent in the period from January to June 1997) was associated with a significant reduction in the rate of adverse cardiac events at one year (from 28.8 percent to 22.8.percent; adjusted relative risk, 0.79; 95 percent confidence interval, 0.69 to 0.90; P<0.001). This reduction in adverse events was exclusively due to a large reduction in subsequent target-vessel revascularization (from 24.4 percent to 17.0 percent; adjusted relative risk, 0.72; 95 percent confidence interval, 0.62 to 0.83; P<0.001) without significant changes in the overall rates of myocardial infarction (5.4 percent, P=0.28) or death (3.9 percent, P=0.65)., Conclusions: The need for target-vessel revascularization during one year of follow-up decreased after percutaneous coronary intervention during the mid-1990s. The reduction was coincident with the introduction and subsequent widespread use of coronary stenting.

Coronary stenting was performed in 15 selected patients with cardiogenic shock, with favorable clinical and angiographic outcomes. This experience suggests that coronary stenting may play an important adjunctive role in the management of cardiogenic shock and may improve outcome beyond that achieved with balloon angioplasty alone.

A cross-sectional survey was conducted to examine current Canadian practices in the nursing and medical management of femoral arterial sheath removal (SR) after PTCA (percutaneous transluminal coronary angioplasty). The purposes of the study were to (a) investigate the roles of the nurses and physicians in SR, (b) assess the length of time arterial sheaths are left in place and patients kept on bedrest, and (c) describe the routine medical protocols used for pain and anticoagulation therapy. Of the 35 hospitals that perform PTCA in Canada, 30 responded to the survey (response rate of 86%). Nurses had primary responsibility for SR in 13% of the sites and shared responsibility with physicians for SR in a further 10% of the institutions. When nurses were trained to remove sheaths, they assumed responsibility for the adjunctive steps to establish hemostasis. One third of hospitals removed sheaths in 4 hours or less; approximately 75% of them removed sheaths in 6 hours or less after PTCA. Patients are kept on bedrest for 6 hours or less following hemostasis in half, and 8 hours or less at three-quarters of the hospitals. Post-PTCA and pre-SR anticoagulant monitoring was used in almost half of the sites. Premedication for SR varied from no premedication to combinations of three intravenous medications plus local anaesthetic. Survey results showed that in almost one quarter of the Canadian institutions where PTCA is performed, nurses play a role in SR. Results also showed that there is no uniformity in post-PTCA SR across Canada and that further research is needed to identify the optimum approach to managing this common cardiovascular procedure.

Objective: To assess the level of use of acetylsalicylic acid (ASA), beta-blockers and thrombolytic therapy--proven efficacious therapies in the management of acute myocardial infarction (AMI)--in contemporary patients admitted with AMI, and to assess the role of contraindications and other patient-specific factors in the use or nonuse of these treatments., Design: The demographics and treatment course of patients admitted with a diagnosis of AMI were reviewed. Specifically targeted therapies were ASA, beta-blockers and thrombolytic therapy. Rates of use were calculated as 'gross utilization' (overall use) and 'adjusted utilization' (accounting for late presentation to hospital, initially equivocal diagnosis or contraindications)., Setting: Tertiary care hospital in suburban Vancouver, British Columbia., Patients: A total of 372 consecutive patients admitted to Royal Columbian Hospital between September 1, 1990 and September 1, 1991., Interventions: None., Main Results: Gross utilization of ASA, beta-blockers and thrombolytic therapy was 71, 31 and 21%, respectively. The adjusted utilization rates for early (6 h or less) treatment with ASA was 66%; with early beta-blockers, it was 18% and was 100% for thrombolytic therapy. Adjusted late (more than 6 h, to hospital discharge) use of ASA and beta-blockers was 84 and 57%, respectively., Conclusions: With the exception of thrombolytic therapy, proven efficacious medical therapies for AMI appear underused at the study hospital. Ongoing educational efforts and continuing patterns of practice analyses are needed.

Quantitative, single voxel proton nuclear magnetic resonance (NMR) spectroscopy and histological analysis was performed in eight dogs implanted with the transplantable canine glioma model of Wodinsky (Proc. Am. Assoc. Cancer Res. 10, 99 (1969)). Signals from choline, creatine, N-Acetyl Aspartate (NAA) and lactate were converted to molar concentration units and correlated with the quantitative analysis of histologically determined tissue types within the localized volume selected for NMR spectroscopy. In general, compared with normal brain, the lesions were associated with reductions in all metabolite concentrations, with the exception of lactate, which was increased. NAA and creatine decreases were most significantly correlated with the total lesion volume (P < 0.01), suggesting that these compounds are present in normal brain only. Changes in choline levels did not correlate strongly with any particular tissue type. Lactate was found to increase with increasing total lesion volume (P < 0.01), but not with increasing percent tumor, suggesting that it accumulates in abnormal tissue other than the tumor. The spectra reported were similar to those observed in human glioblastomas, with the exception that elevations of choline were not observed. The transplantable canine gliosarcoma system appears to be a suitable tumor model for evaluation by clinical radiological techniques such as magnetic resonance imaging (MRI) and proton NMR spectroscopy.

Cold potassium cardioplegia provides adequate protection for coronary bypass operations, but severe coronary stenoses limit cardioplegic delivery to ischemic regions. The traditional technique delivers cardioplegic solution into the aortic root during the performance of distal anastomoses. The proposed alternative technique constructs proximal as well as distal anastomoses during a prolonged cross-clamp period, but permits more uniform cooling. The two techniques were compared in a prospective concurrent trial of 45 patients undergoing elective coronary bypass grafting. The traditional technique was employed in 26 patients (Group A) and the alternative technique in 19 patients (Group B). In both groups, 700 to 1,000 ml of a crystalloid cardioplegic solution was infused into the aortic root after application of the aortic cross-clamp. In Group A (traditional technique), 500 ml was infused into the aortic root after each distal anastomosis. In Group B (alternative technique), cardioplegic solution was administered through the vein graft after each distal anastomosis, and a proximal anastomosis was constructed after distal anastomoses to the most ischemic regions to permit continued cardioplegic delivery to these regions. The cross-clamp period was shorter in Group A than in Group B (44 +/- 15 versus 60 +/- 18 minutes, p less than 0.01), but the mean temperature in the most ischemic region was warmer (Group A, 19 degrees +/- 3 degrees C; Group B, 15 degrees +/- 3 degrees C, p less than 0.05). The postoperative CK-MB was higher in Group A (Group A, 47 +/- 36; Group B, 21 +/- 9 IU/L, p less than 0.01). Cardiac lactate production persisted longer in Group A (Group A, 4 +/- 1; Group B, 1 +/- 1 hours postoperatively, p less than 0.05). Volume loading 4 hours postoperatively produced a similar increase in left atrial pressure and cardiac index in both groups. In response to volume loading, Group A patients produced lactate, but Group B patients extracted lactate (change in cardiac lactate extraction: Group A, -1.7 +/- 2.3; Group B, +2.5 +/- 5.1 mg/dl, p less than 0.05). The construction of proximal as well as distal anastomoses during a prolonged cross-clamp period permits more uniform cooling and immediate reperfusion. This alternative technique resulted in less injury (CK-MB release) and more rapid recovery of myocardial metabolism.

Although cold potassium cardioplegia provides adequate myocardial protection, transient hemodynamic and metabolic instability occasionally occurs after uncomplicated coronary bypass surgery. Two methods to increase cardiac output were compared 2 to 6 hours postoperatively in 24 patients recovering from elective coronary bypass operation. Volume loading increased cardiac index (CI) from 2.1 +/- 0.5 to 2.7 +/- 0.6 L/min/m2 by increasing left atrial pressure (LAP) from 8.6 +/- 3.6 to 13.0 +/- 4.1 mm Hg. Atrial pacing at a rate of 112 +/- 8 beats per minute increased CI from 2.4 +/- 0.5 to 2.7 +/- 0.8 L/min/m2 without a change in LAP. Ejection fraction by nuclear angiography did not change, but the calculated left ventricular end-diastolic volume index (stroke index/ejection fraction) increased with volume loading and decreased with atrial pacing--a decrease in diastolic compliance. Myocardial oxygen extraction did not change, but myocardial lactate extraction increased with volume loading and decreased with atrial pacing. Coronary sinus blood flow was measured in 5 patients and increased with both methods studied. Volume loading demonstrated that myocardial performance was normal and myocardial metabolism increased commensurate with the increase in work. Atrial pacing increased CI but resulted in anaerobic metabolism and a decrease in diastolic compliance. Volume loading rather than atrial pacing will improve CI without producing ischemia in the early postoperative period.

Left ventricular function at rest and during supine bicycle exercise was assessed by gated radionuclide angiography in 20 diabetic patients and 18 normal control subjects without clinical evidence of heart disease. The diabetic patients were aged 21 to 44 years and all except one used insulin. No subject developed chest pain or electrocardiographic changes during exercise. Both groups had a similar rest and exercise heart rate and blood pressure, and both achieved similar work loads. The control group had an ejection fraction at rest of 65.4 +/- 6.2% (mean +/- SD) and only 1 of 18 showed a decrease with exercise; peak exercise ejection fraction averaged 77.1 +/- 7.8%. The diabetic group had a mean ejection fraction at rest of 63.7 +/- 6.5%, similar to that of the control group, but 7 of 20 showed a decrease during exercise; the exercise ejection fraction averaged 67.7 +/- 9.7%, significantly lower than that of the control group (p less than 0.01). The diabetic patients varied widely in ejection fraction response to exercise, ranging from an increase of 25% to a decrease of 21%. This response did not correlate with age, sex, duration of diabetes, smoking, retinopathy, exercise heart rate, blood pressure or rate-pressure product, work load attained or ejection fraction at rest. These data suggest that approximately one-third of patients with diabetes have subclinical left ventricular dysfunction without correlation to risk factors for atherosclerosis or other diabetic complications. Whether this is due to unrecognized coronary artery disease or primary myocardial disease remains unknown.

Long-term follow-up of aortocoronary bypass has shown good preservation of ventricular function. However, myocardial reserve in the immediate postoperative period may not be optimal. Nineteen patients who underwent elective aortocoronary bypass protected with cold potassium cardioplegia were studied in the early postoperative period at rest and during the stress of atrial and ventricular pacing. Performance was assessed by hemodynamic, metabolic and nuclear angiographic measurements. In the first 2--6 hours after aortic cross clamping, myocardial performance was preserved at rest and there was no evidence of ischemic metabolism. Atrial pacing at a rate of 119 beats/min caused a significant increase in cardiac index (p less than 0.01) without deterioration in hemodynamics, ejection fraction or metabolic status. At the same rate, ventricular pacing did not change the cardiac index and there was a decrease in hemodynamic function. Ejection fraction decreased from 56% to 44% (p less than 0.05) without a change in end-diastolic volume. Lactate, pyruvate and beta hydroxybutyrate extractions were changed to net production. Ventricular performance was preserved at rest immediately after aortocoronary bypass done with multidose cold potassium cardioplegia, with adequate reserve to meet the stress of atrial but not ventricular pacing. We conclude that the therapeutic implications of the type of pacing selected in the immediate postoperative period may be important.

Left ventricular function was compared in 18 normal sedentary controls (mean age 28 years, range 22 - 34 years) and nine endurance-trained athletes (mean age 19 years, range 15 - 25 years) at rest and during supine bicycle exercise. Gated radionuclide angiocardiograms were performed at rest and at each level of graded maximal supine bicycle exercise. Heart rate, blood pressure, left ventricular ejection fraction and the relative changes in left ventricular end-diastolic and end-systolic volumes were assessed. Athletes attained a much greater work load than controls (mean 22.1 kpm/kg body weight vs 13 kpm/Kg body weight). Both groups achieved similar increased in heart rate, blood pressure and ejection fractions. In the controls, the mean end-diastolic volume increased to 124% of that at rest (p less than 0.02) during exercise and the mean end-systolic volume decreased to 81% of the rest level (p less than 0.02). In contrast, the mean end-diastolic volume did not significantly change during exercise in the athletes, and the mean end-systolic volume decreased to 64% of rest (p less than 0.05). Thus, although trained and untrained healthy subjects had similar increases in the left ventricular ejection fraction during exercise, different mechanisms were used to achieve these increases. Untrained subjects increased end-diastolic volumes, whereas trained subjects decreased the end-systolic volumes. The ability of athletes to exercise without increasing preload may be an effect of training amd might have important implications in reducing myocardial oxygen demand during exercise.

Intravenous infusions are required to maintain ventricular preload after uneventful coronary bypass operation. During the early postoperative period, when myocardial metabolic recovery is incomplete, volume loading is intended to stabilize ventricular function and metabolism and to prevent progressive ischemic injury. This study attempts to define the optimal preload for both metabolism and performance. Thirty-seven patients recovering from elective coronary bypass operations and cold potassium cardioplegia underwent volume loading with whole plasma. The initial response (VLA) from a low left atrial pressure (LAP = 7.3 +/- 3.3 mm Hg) was compared with the subsequent response (VLB) from a higher filling pressure (LAP = 10.9 +/- 2.7 mm Hg). Both VLA and VLB produced a similar increase in cardiac index, stroke work index, and end-diastolic volume index (EDVI), and a decrease in ejection fraction (measured by nuclear angiography). Myocardial lactate extraction increased with VLA, but myocardial lactate production resulted with VLB. A careful analysis of these volume loading studies suggested that myocardial performance and compliance were not altered in the early postoperative period. The decrease in ejection fraction with volume loading may have resulted from a combination of increased wall tension and decreased inotropic stimulation. After uneventful coronary bypass surgery, an LAP between 5 and 12 mm Hg corresponded to an EDVI between 30 and 80 ml/m2 and produced adequate cardiac index, stroke work index, and lactate extraction. A lower or higher preload did not improve function and resulted in abnormal metabolism.

Coronary bypass performed with moderate systemic hypothermia (25 degrees C) and cold-potassium cardioplegia was associated with a fall and subsequent rise in core (pulmonary arterial) temperature. Serial hemodynamic measurements during rewarming and recovery revealed a decrease in cardiac index (CI) without a decrease in the left atrial pressure (LAP) of 17 patients recovering from uneventful coronary bypass surgery. Nuclear ventriculograms performed during rewarming demonstrated a decrease in left ventricular end-diastolic volume index (EDVI, calculated from the thermodilution stroke index divided by the nuclear ejection fraction) without a change in LAP. Volume loading during both mild hypothermia (35 +/- 5[SD]degrees C) and normothermia revealed that myocardial performance (the relation between CI and EDVI) was unchanged, but diastolic compliance (the relation between LAP and EDVI) decreased with rewarming. LAP was a poor indicator of left ventricular preload (EDVI) during rewarming, and volume loading was required to maintain preload and prevent hypoperfusion.

Rest and exercise right and left ventricular function were compared using equilibrium gated radionuclide angiography in 19 normal sedentary control subjects (mean age 28 years, range 22 to 34) and 34 patients with hemodynamically documented congenital ventricular septal defect (VSD) (mean age 27 years, range 20 to 40). The 34 patients with VSD were divided into 3 groups: those in Group 1 (17 patients) had pulmonary to systemic blood flow ratios of less than 2 to 1; those in Group 2 (12 patients) had prior surgical closure of VSD (mean interval from surgery 17 years, range 9 to 22), and those in Group 3 (5 patients) had Eisenmenger's complex. Gated radionuclide angiography was performed at rest and during each level of graded supine bicycle exercise to fatigue. Heart rate, blood pressure, maximal work load achieved, and right and left ventricular ejection fractions were assessed. The control subjects demonstrated an increase in both the left and right ventricular ejection fractions with exercise (0.70 +/- 0.07 to 0.79 +/- 0.05 and 0.46 +/- 0.06 to 0.57 +/- 0.04; p less than 0.001 for left and right ventricles, respectively). All study groups failed to demonstrate an increase in ejection fraction in either ventricle with exercise. Furthermore, resting left ventricular ejection fraction in Groups 2 and 3 was lower than that in the control subjects (0.59 +/- 0.09 and 0.54 +/- 0.06 versus 0.70 +/- 0.07; p less than 0.001) and resting right ventricular ejection fraction was lower in Group 3 versus control subjects (0.30 +/- 0.07 versus 0.46 +/- 0.06; p less than 0.001). Thus (1) left and right ventricular function on exercise were abnormal in patients with residual VSD as compared with control subjects; (2) rest and exercise left ventricular ejection fractions remained abnormal despite surgical closure of VSD in the remote past; (3) resting left and right ventricular function was abnormal in patients with Eisenmenger's complex; (4) lifelong volume overload may be detrimental to myocardial function.