bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with serum ACE concentration and increased risk for CAD in the Japanese.
Authors: Nakai K , Itoh C , Miura Y , Hotta K , Musha T , Itoh T , Miyakawa T , Iwasaki R , Hiramori K 
Published: June 2012

BACKGROUND
The angiotensin I-converting enzyme (ACE) is a key component of the renin-angiotensin system thought to be important in the pathogenesis of hypertension and cardiovascular disease. Deletion polymorphism in the ACE gene may be a risk factor for myocardial infarction in the Caucasian population. However, this finding has not yet been investigated in the Japanese population.

METHODS AND RESULTS
A 287-bp insertion/deletion polymorphism in intron 16 of the ACE gene was examined by polymerase chain reaction in a cross-sectional study of 100 healthy subjects and 178 patients with coronary artery disease (CAD) (70 angina pectoris, 108 myocardial infarction), whose serum ACE levels were concomitantly measured. Polymorphism of the ACE gene was characterized by three genotypes: two deletion alleles (genotype DD), two insertion alleles (genotype II), and heterozygous alleles (genotype ID). No differences could be detected among the three genotypes for total cholesterol, HDL cholesterol, and body mass index. Serum ACE levels were 11.4 +/- 2.7, 14.5 +/- 3.5, and 16.6 +/- 4.6 IU/mL for genotypes II, ID, and DD, respectively. In the study population, the genotype DD was more closely associated with CAD than the other two genotypes (ID and II). The frequency of deletion alleles was higher (0.58) in the CAD group than in healthy control subjects (0.42) (P < .05). Furthermore, multivessel disease was more strongly associated with deletion alleles than with insertion alleles (P < .05).

CONCLUSIONS
A deletion polymorphism of the ACE gene is associated with serum ACE activity and increased risk for CAD in the Japanese.
Alterations in muscarinic K+ channel response to acetylcholine and to G protein-mediated activation in atrial myocytes isolated from failing human hearts.
Authors: Koumi S , Arentzen C E , Backer C L , Wasserstrom J A 
Published: June 2012

BACKGROUND
A variety of previous studies have demonstrated reduced diastolic potential and electrical activity in atrial specimens from patients with heart disease. Although K+ channels play a major role in determining resting membrane potential and repolarization of the action potential, little is known about the effects of preexisting heart disease on human atrial K+ channel activity.

METHODS AND RESULTS
We characterized the inwardly rectifying K+ channel (IKI) and the muscarinic K+ channel [IK(ACh)] in atrial myocytes isolated from patients with heart failure (HF) and compared electrophysiological characteristics with those from donors (control) by the patch-clamp technique. Resting membrane potentials of isolated atrial myocytes from HF were more depolarized (-51.1 +/- 9.7 mV, mean +/- SD, n = 30 patients) than those from donors (-73.0 +/- 7.2 mV, n = 4 patients, P < .001). The action potential duration in HF was longer than that in donors. Although acetylcholine (ACh) shortened the action potential, reduced the overshoot, and hyperpolarized the atrial cell membrane in HF, these effects were attenuated compared with those observed in donors. The whole-cell membrane current slope conductance in HF was small, the reversal potential was more positive, and the sensitivity to ACh was less compared with donors. In single-channel recordings from cell-attached patches, IK1 channel conductance and gating characteristics were the same in HF and donor atria. When ACh was included in the pipette solution, IK(ACh) was activated in both groups. Single-channel slope conductance of IK(ACh) averaged 42 +/- 3 pS (n = 28) in HF and 44 +/- 2 pS (n = 4) in donors, and mean open lifetime was 1.3 +/- 0.3 milliseconds (n = 24) in HF and 1.5 +/- 0.4 milliseconds (n = 4) in donors. These values were virtually identical in the two groups (not significantly different, NS), although both single IK1 and IK(ACh) channel densities were less in HF. Channel open probability of IK(ACh) was also less in HF (4.0 +/- 1.2%, n = 24) than in donors (6.8 +/- 1.1%, n = 3, P < .01). The concentration of ACh at half-maximal activation was 0.11 mumol/L in HF and 0.03 mumol/L in donors. In excised inside-out patches, IK(ACh) from HF required higher concentrations of GTP and GTP gamma S to activate the channel compared with donors. These results suggest a reduced IK(ACh) channel sensitivity to M2 cholinergic receptor-linked G protein (Gi) in HF compared with donors.

CONCLUSIONS
Atrial myocytes isolated from failing human hearts exhibited a lower resting membrane potential and reduced sensitivity to ACh compared with donor atria. Whole-cell and single-channel measurements suggest that these alterations are caused by reduced IK1 and IK(ACh) channel density and reduced IK(ACh) channel sensitivity to Gi-mediated channel activation in HF.
Hemodynamic and metabolic effects of paced linkage following heterotopic cardiac transplantation.
Authors: Morris-Thurgood J , Cowell R , Paul V , Kalsi K , Seymour A M , Ilsley C , Mitchell A , Khaghani A , Yacoub M 
Published: June 2012

BACKGROUND AND PURPOSE
Heterotopic cardiac transplantation is a valuable surgical technique that maximizes the use of donor organs. However, recipient heart function may decline steadily postoperatively with resulting clinical deterioration. Paced linkage has the potential of reducing afterload and enhancing coronary flow of both hearts, thereby improving recipient- and donor-heart function. This may have long-term as well as short-term benefits.

METHODS AND RESULTS
The study was performed on 11 heterotopic transplant recipients. The two hearts were linked with a pacemaker (paced linkage) to produce recipient heart systole during different periods of donor-heart diastole. The recipient ventricular contraction was timed to occur during early, mid, and late diastole of the donor heart. Hemodynamic baseline measurements were compared with the optimal counterpulsated data. Paced linkage produced significant improvements in total cardiac output, 5.0 +/- 0.9 compared with baseline 4.5 +/- 0.8 L/min (P = .021); recipient coronary sinus flow, 278 +/- 145 versus 186 +/- 108 mL/min (P = .022); and aortic systolic pressure, 135 +/- 27 versus 123 +/- 27 mm Hg (P = .005). There was an overall improvement in systolic ventricular performance in the recipient heart when pace linked, as evidenced by a significant increase in left ventricular systolic pressure of 118 +/- 36 compared with the baseline value of 108 +/- 33 mm Hg (P = .016), an increase in ejection period from 174 +/- 30 versus 203 +/- 48 (P = .046), and a decrease in the pre-ejection period of 147 +/- 37 when paced versus 181 +/- 39 milliseconds (P = .013). The metabolic studies showed a significant decrease in hypoxanthine release from a baseline level of 0.4 mumol/L to a paced value of -0.06 mumol/L (P = .002); these very low values would suggest that there is no evidence of ischemia. Hemodynamic changes in the donor heart included a significant reduction in the left ventricular end-diastolic pressure from 6.8 +/- 4.4 versus baseline of 10.5 +/- 5.8 mm Hg (P = .029) and in maximum -dP/dT from 3.2 +/- 1.7 versus baseline of 2.1 +/- 1.1.

CONCLUSIONS
Paced linkage after heterotopic cardiac transplant produces significant functional improvements in both hearts. Permanent pacemaker implantation may sustain these acute benefits and prevent the premature deterioration of the recipient heart.
Nonuniform course of left ventricular pressure fall and its regulation by load and contractile state.
Authors: Leite-Moreira A F , Gillebert T C 
Published: June 2012

BACKGROUND
Effects of systolic left ventricular pressure (LVP) on rates of pressure fall remain incompletely understood. This study analyzed phase-plane dP/dt versus LVP plots to differentiate between accelerating and decelerating effects and to investigate the variability in reported load effects on rates of LVP fall.

METHODS AND RESULTS
Abrupt aortic occlusions were performed by inflating a balloon positioned in the ascending aorta of anesthetized open-chest dogs (n = 17). The occlusions resulted in clamp elevations of systolic LVP. In protocol A, the elevations of systolic LVP induced by total aortic occlusions were timed at early, mid, and late ejection. The magnitude of the elevations was 36.0 +/- 3.6 mm Hg for early, 11.6 +/- 0.6 mm Hg for mid, and negligible for late occlusions. The course of LVP fall appeared to be more complex than previously appreciated. Pressure fall might be subdivided in an initial accelerative phase, an intermediate decelerative phase, and a terminal decelerative phase. The initial phase accelerated with mid and late occlusions. The intermediate phase slowed down with early and to a lesser extent with mid occlusions. The terminal phase was never affected by aortic clamp occlusions. In protocol B, early elevations of systolic LVP were obtained with multiple graded aortic occlusions. The effects of matched LVP elevations of 12 mm Hg on rate of LVP fall were evaluated with the time constant of LVP fall (tau) and showed an interanimal variability ranging from acceleration and a 20% decrease in tau to deceleration and a 35% increase in tau. Changes in tau were moderately correlated with commonly used indexes of contractility (peak +dP/dt, r = -.78; regional fractional shortening, r = -.63). These changes in tau showed a close correlation with the systolic LVP of the test beat, expressed as a percentage of the peak isovolumetric LVP, obtained with total aortic occlusion (r = .984). This suggested that the contraction-relaxation coupling should be analyzed in terms of peak force development rather than contraction velocity or ejection fraction.

CONCLUSIONS
LVP fall could be subdivided into an initial accelerative phase, an intermediate decelerative phase, and a terminal decelerative phase. Effects of elevations in systolic LVP on rate of LVP fall could be predicted by knowing peak isovolumetric LVP. Nonuniformity of LVP fall and adequate interpretation of load effects should be taken into account when clinical situations or pharmacological interventions are considered. In congestive heart failure, slow LVP fall could mainly reflect working conditions close to isovolumetric rather than relaxation disturbances.
Mortality within 24 hours of thrombolysis for myocardial infarction. The importance of early reperfusion. The GUSTO Investigators, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.
Authors: Kleiman N S , White H D , Ohman E M , Ross A M , Woodlief L H , Califf R M , Holmes D R , Bates E , Pfisterer M , Vahanian A 
Published: June 2012

BACKGROUND
A paradoxical increased risk of death has been reported during the first 24 hours after thrombolysis for myocardial infarction. The mechanism of this phenomenon is not known, nor is its relation to the success or failure of reperfusion. The present study was a prospectively designed analysis of deaths occurring within the first 24 hours in the GUSTO trial.

METHODS AND RESULTS
There were 41,021 patients enrolled in GUSTO, a randomized comparison of streptokinase with intravenous or subcutaneous heparin, accelerated tissue-type plasminogen activator (TPA), and combination of streptokinase and TPA. An angiographic mechanistic substudy examined reperfusion (using the TIMI flow grading criteria) 90 minutes after the assigned thrombolytic regimen was begun in 1567 patients. There were 1125 deaths (2.8%) within 24 hours ("early deaths") and 1726 additional deaths (4.2%) after 24 hours but within 30 days ("later deaths"). At the time of presentation, the most potent predictors of early death were hypotension and sinus tachycardia. In a multiple logistic regression model, lower systolic blood pressure, shorter height, higher heart rate, and the absence of prior smoking distinguished early death from later death. Reinfarction occurred in 26 patients (2.4%), shock in 572 patients (52%), atrioventricular block in 308 patients (28%), and tamponade in 106 patients (10%) dying early compared with 262 (15%), 788 (46%), 396 (23%), and 74 (4%) respective patients dying later. There were no differences in early mortality among the thrombolytic regimens for the first 6 hours after randomization. By 24 hours, however, mortality was 2.89% for streptokinase recipients, 2.84% for combination therapy recipients, and 2.36% for accelerated TPA recipients (P = .005). There was little difference among patients with differing flow grades in the infarct artery during the first 4 hours, although mortality was 2.35% for patients with flow grade 0 or 1, 2.92% for patients with flow grade 2, and 0.89% for patients with flow grade 3.

CONCLUSIONS
Even with aggressive management regimens, mortality within the first 24 hours accounted for a large proportion of postthrombolytic deaths. Patients dying early were more likely to present with pump failure than were those dying later and were more likely to diet of events related to left ventricular dysfunction, although cardiac tamponade also accounted for a significant minority of these deaths. Thus, the severity of the clinical presentation rather than the underlying risk factors predicts early mortality. Based on the angiographic substudy data, it appears that rather than hastening early mortality, successful restoration of complete antegrade flow in the infarct-related artery protects against early death.
Activation of complement and kinin systems after thrombolytic therapy in patients with acute myocardial infarction. A comparison between streptokinase and recombinant tissue-type plasminogen activator.
Authors: Agostoni A , Gardinali M , Frangi D , Cafaro C , Conciato L , Sponzilli C , Salvioni A , Cugno M , Cicardi M 
Published: June 2012

BACKGROUND
We have previously shown that treatment with streptokinase induces abrupt complement activation and transient neutropenia in patients with acute myocardial infarction (AMI). The purpose of this study was to compare the effects of two different thrombolytic agents--streptokinase (SK) and recombinant tissue-type plasminogen activator (rTPA)--on activation of the complement and kinin systems in plasma of patients with AMI.

METHODS AND RESULTS
Forty-one patients with AMI who were eligible for thrombolytic therapy were studied. Twenty-three patients were treated with streptokinase (1.5 million IU IV over 60 minutes) and 18 were treated with rTPA (8 with bolus of 10 mg IV, followed by 50 mg infused over 60 minutes and then 40 mg infused over 120 minutes; 10 patients were administered rTPA and heparin according to the accelerated infusion protocol indicated by the GUSTO study). C4a and C3a were measured by radioimmunoassay, soluble terminal complement components (SC5b-9) and anti-SK IgG antibodies were measured by ELISA. Cleaved high molecular weight kininogen (HK) was quantitated in plasma by SDS-PAGE and immunoblotting analysis. C4a levels were significantly and similarly increased in both groups, whereas the levels of C3a and SC5b-9 after rTPA infusion were only slightly elevated and were significantly lower than after SK. No differences were observed between patients treated with slow or accelerated rTPA regimens. The titer of antibodies to SK was highly correlated with the levels of C3a and SC5b-9, whereas a lesser correlation was observed with C4a. Treatment with rTPA did not induce the transient neutropenia observed after SK infusion. The cleavage products of HK were significantly greater after SK than after rTPA infusion.

CONCLUSIONS
Our results show that both thrombolytic agents activate the classic complement pathway and that plasmin could be the common trigger for this phenomenon. A significant activation of the complement common pathway (from C3 to terminal components) was observed only with SK infusion and is attributable to the rapid formation of immunocomplexes between SK and anti-SK antibodies present in plasma as a consequence of previous streptococcal infections. The minimal activation of C5 component of the common pathway explains the absence of leukopenia in patients treated with rTPA. Cleavage of HK, larger after SK than after rTPA infusion, represents a condition enhancing the generation of bradykinin by kallikrein. The recent experimental data that indicate a damaging effect of complement activation on the infarcted zone and the contrasting favorable effect consequent to bradykinin formation raise some questions about the clinical importance of the different biological consequences of SK versus rTPA.
Fibrin formation and degradation in patients with arteriosclerotic disease.
Authors: Herren T , Stricker H , Haeberli A , Do D D , Straub P W 
Published: June 2012

BACKGROUND
The blood coagulation cascade was reported to be activated in patients with arteriosclerotic disease of the lower limbs (peripheral arterial disease, PAD). There is more thrombin and fibrin formation compared with healthy control subjects. In many studies, however, the presence of arteriosclerotic disease had not been thoroughly ruled out in the control group. Therefore, markers of the activation of the blood coagulation cascade were measured in patients with PAD and in a carefully defined control group, both groups being subjected to an exercise test.

METHODS AND RESULTS
Twenty-two patients with angiographically documented PAD of grade II (Fontaine classification) and 13 control subjects in whom the presence of arteriosclerotic lesions was ruled out by noninvasive means in the carotid arteries, abdominal aorta, leg arteries, and coronary arteries took part in the study. Before and immediately after a treadmill stress test, the concentrations of prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), fibrinopeptide A (FPA; this peptide was measured in spot urine also), and D-dimers were measured. Before exercise, the concentrations of F1 + 2 (1.0 +/- 0.6 versus 0.7 +/- 0.3 nmol/L), TAT (2.9 +/- 2.1 versus 1.9 +/- 0.8 micrograms/L), and D-dimers (318.2 +/- 270.1 versus 150.0 +/- 91.4 micrograms/L) were significantly higher in the patients with PAD compared with the healthy control subjects. FPA concentrations in plasma (1.9 +/- 1.0 versus 1.4 +/- 0.6 micrograms/L) and spot urine were not different, however. F1 + 2, FPA, and D-dimer concentrations correlated with the severity of the PAD as assessed by the ankle systolic blood pressure index (ABPI). The symptom-limited stress test did not lead to further activation of the blood coagulation cascade. However, concentrations of F1 + 2 (P < .001) and TAT (P < .01) after exercise correlated with the presence of ischemic changes in the stress-test ECG.

CONCLUSIONS
There is evidence of enhanced thrombin formation in patients with PAD compared with an age- and sex-matched control group without clinical and sonographic evidence of arteriosclerosis. The thrombin formed, however, appears to be almost completely neutralized by antithrombin III. No direct evidence of fibrin formation was obtained, since the FPA concentrations were not different. In the patients with PAD, the higher concentrations of D-dimers are indicative of in vivo fibrinolysis. Thus, some fibrin formation must be postulated to occur in patients with arteriosclerosis.
Reduced peak aerobic capacity in asymptomatic left ventricular systolic dysfunction. A substudy of the studies of left ventricular dysfunction (SOLVD). SOLVD Investigator. Studies of Left Ventricular Dysfunction.
Authors: LeJemtel T H , Liang C S , Stewart D K , Kirlin P C , McIntyre K M , Robertson T H , Moore A , Cahill L , Galvao M , Wellington K L 
Published: June 2012

BACKGROUND
Peak oxygen consumption is reduced in patients with symptomatic congestive heart failure, but functional capacity of patients with asymptomatic left ventricular systolic dysfunction has not been assessed by measurement of peak oxygen consumption attained during graded exercise testing.

METHODS AND RESULTS
Peak oxygen consumption, that is, aerobic capacity (VO2, mL/kg per minute), was determined during graded treadmill exercise using the modified Naughton protocol in 40 patients with left ventricular systolic dysfunction (mean ejection fraction ranging from 14% to 35%; mean, 29%) who, while not receiving any cardiac medications, were totally asymptomatic, and in 41 age-matched normal subjects. Peak exercise duration and VO2 were significantly lower in patients with asymptomatic left ventricular systolic dysfunction than in normal subjects (948 +/- 273 versus 1239 +/- 372 seconds, P < .001, and 22.1 +/- 5.9 versus 29.8 +/- 7.7 mL/kg per minute, respectively, P < .001), while asymptomatic patients and normal subjects reached similar respiratory equivalents (1.14 +/- 0.11 versus 1.11 +/- 0.11 [NS]) and level of perceived exertion, using the modified Borg scale (7.4 +/- 2.6 versus 8.1 +/- 1.5 [NS]). Heart rate, systemic blood pressure, and oxygen pulse response to peak exercise were significantly lower in asymptomatic patients than in normal subjects.

CONCLUSIONS
Although patients with left ventricular systolic dysfunction can be totally asymptomatic in their daily activities, they have experienced a substantial reduction in peak aerobic capacity when compared with normal subjects of similar age.