Percutaneous, non-surgical placement of tunneled, cuffed, external jugular hemodialysis catheters: a case report.

The right internal jugular vein is widely accepted as the vessel of choice for placement of long-term central venous catheters for hemodialysis. As vascular access sites become progressively depleted, alternate anatomic locations for access must be sought. We describe a non-surgical (fluoroscopy assisted, percutaneous) technique for placement of external jugular, tunneled, cuffed hemodialysis catheters, and provide long-term blood flow and dialysis adequacy data for EJV catheters.

Reduction in density of transverse tubules and L-type Ca(2+) channels in canine tachycardia-induced heart failure.

OBJECTIVE: Persistent supraventricular tachycardia leads to the development of a dilated cardiomyopathy with impairment of excitation-contraction (EC) coupling. Since the initial trigger for EC coupling in ventricular muscle is the influx of Ca(2+) through L-type Ca(2+) channels (I(Ca)) in the transverse tubules (T-tubules), we determined if the density of the T-tubule system and L-type Ca(2+) channels change in canine tachycardia pacing-induced cardiomyopathy. METHODS: Confocal imaging of isolated ventricular myocytes stained with the membrane dye Di-8-ANEPPS was used to image the T-tubule system, and standard whole-cell patch clamp techniques were used to measure I(Ca) and intramembrane charge movement. RESULTS: A complex staining pattern of interconnected tubules including prominent transverse components spaced every approximately 1.6 microm was present in control ventricular myocytes, but failing cells demonstrated a far less regular T-tubule system with a relative loss of T-tubules. In confocal optical slices, the average % of the total cell area staining for T-tubules decreased from 11.5+/-0.4 in control to 8.7+/-0.4% in failing cells (P<0.001). Whole-cell patch clamp studies revealed that I(Ca) density was unchanged. Since whole-cell I(Ca) is due to both the number of channels as well as the functional properties of those channels, we measured intramembrane charge movement as an assay for changes in channel number. The saturating amount of charge that moves due to gating of L-type Ca(2+) channels, Q(on,max), was decreased from 6.5+/-0.6 in control to 2.8+/-0.3 fC/pF in failing myocytes (P<0.001). CONCLUSIONS: Cellular remodeling in heart failure results in decreased density of T-tubules and L-type Ca(2+) channels, which contribute to abnormal EC coupling.

Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.

BACKGROUND: Inherited mutations cause approximately 35 percent of cases of dilated cardiomyopathy; however, few genes associated with this disease have been identified. Previously, we located a gene defect that was responsible for autosomal dominant dilated cardiomyopathy and conduction-system disease on chromosome 1p1-q21, where nuclear-envelope proteins lamin A and lamin C are encoded by the LMNA (lamin A/C) gene. Mutations in the head or tail domain of this gene cause Emery-Dreifuss muscular dystrophy, a childhood-onset disease characterized by joint contractures and in some cases by abnormalities of cardiac conduction during adulthood. METHODS: We evaluated 11 families with autosomal dominant dilated cardiomyopathy and conduction-system disease. Sequences of the lamin A/C exons were determined in probands from each family, and variants were confirmed by restriction-enzyme digestion. The genotypes of the family members were ascertained. RESULTS: Five novel missense mutations were identified: four in the alpha-helical-rod domain of the lamin A/C gene, and one in the lamin C tail domain. Each mutation caused heritable, progressive conduction-system disease (sinus bradycardia, atrioventricular conduction block, or atrial arrhythmias) and dilated cardiomyopathy. Heart failure and sudden death occurred frequently within these families. No family members with mutations had either joint contractures or skeletal myopathy. Serum creatine kinase levels were normal in family members with mutations of the lamin rod but mildly elevated in some family members with a defect in the tail domain of lamin C. CONCLUSIONS: Genetic defects in distinct domains of the nuclear-envelope proteins lamin A and lamin C selectively cause dilated cardiomyopathy with conduction-system disease or autosomal dominant Emery-Dreifuss muscular dystrophy. Missense mutations in the rod domain of the lamin A/C gene provide a genetic cause for dilated cardiomyopathy and indicate that this intermediate filament protein has an important role in cardiac conduction and contractility.

Force-velocity and power-load curves in rat skinned cardiac myocytes.

1. This study utilized a skinned myocyte preparation with low end compliance to examine force-velocity and power-load curves at 12 C in myocytes from rat hearts. 2. In maximally activated myocyte preparations, shortening velocities appeared to remain constant during load clamps in which shortening took place over a sarcomere length range of approximately 2.30-2.00 micro m. These results suggest that previously reported curvilinear length traces during load clamps of multicellular preparations were due in part to extracellular viscoelastic structures that give rise to restoring forces during myocardial shortening. 3. During submaximal Ca2+ activations, the velocity of shortening at low loads slowed and the time course of shortening became curvilinear, i.e. velocity progressively slowed as shortening continued. This result implies that cross-bridge cycling kinetics are slower at low levels of activation and that an internal load arises during shortening of submaximally activated myocytes, perhaps due to slowly detaching cross-bridges. 4. Reduced levels of activator Ca2+ also reduced maximal power output and increased the relative load at which power output was optimal. For a given absolute load, the shift has the effect of maintaining power output near the optimum level despite reductions in cross-bridge number and force generating capability at lower levels of Ca2+.

Sarcomere length dependence of the rate of tension redevelopment and submaximal tension in rat and rabbit skinned skeletal muscle fibres.

1. We examined the hypothesis that in skeletal muscle the steep relationship between twitch tension and sarcomere length (SL) within the range 2.30 to 1.85 microns involves SL-dependent alterations in the rate of tension development. 2. In skinned preparations of both rat slow-twitch and rabbit fast-twitch skeletal muscle fibres the rate of tension redevelopment (ktr) at 15 degrees C was reduced at short SL (approximately 2.00 microns) compared with a longer SL (approximately 2.30 microns). In submaximally activated fibres, the decrease in ktr over this range of lengths was greater in fast-twitch fibres (38% reduction) than in slow-twitch fibres (14% reduction). 3. Ca2+ sensitivity of tension, as assessed as the pCa (-log[Ca2+]) for half-maximal activation, or pCa50, decreased to a greater extent in rabbit fast-twitch skeletal muscle fibres than in slow-twitch fibres from both rabbit and rat when SL was reduced from approximately 2.30 to approximately 1.85 microns. The delta pCa50 over this SL range was 0.24 +/- 0.07 pCa units in fast-twitch fibres from rabbit psoas muscle. The delta pCa50 for slow-twitch fibres from rabbit and rat soleus muscle was 0.08 +/- 0.02 and 0.10 +/- 0.04 pCa units, respectively. 4. Osmotic compression of both slow-twitch and fast-twitch fibres at a SL of 2.00 microns increased ktr to values similar to those obtained at a SL of 2.30 microns in the absence of dextran. This result indicates that the slower rate of tension redevelopment at short SL is due in large part to the increase in interfilament lattice spacing associated with shorter SL. 5. Taken together, these results suggest that length dependence of twitch tension is, in part, due to length dependence of isometric cross-bridge interaction kinetics, an effect that is mediated by length-dependent changes in interfilament lattice spacing.

Ca2+ binding to troponin C in skinned skeletal muscle fibers assessed with caged Ca2+ and a Ca2+ fluorophore. Invariance of Ca2+ binding as a function of sarcomere length.

Ca2+ sensitivity of tension varies with sarcomere length in both skeletal and cardiac muscles. One possible explanation for this effect is that the Ca2+ affinity of the regulatory protein troponin C decreases when sarcomere length is reduced. To examine length dependence of Ca2+ binding to troponin C in skeletal muscle, we developed a protocol to simultaneously monitor changes in sarcomere length, tension, and Ca2+ concentration following flash photolysis of caged Ca2+. In this protocol, [Ca2+] was rapidly increased by flash photolysis of caged Ca2+, and changes in [Ca2+] due to photolysis and the subsequent binding to troponin C were assessed using a Ca2+ fluorophore. Small bundles of fibers from rabbit skinned psoas muscles were loaded with Ca2+ fluorophore (Fluo-3) and caged Ca2+ (dimethoxynitrophenamine or o-nitrophenyl-EGTA). The bundles were then transferred to silicone oil, where [Ca2+]free, tension, and sarcomere length were monitored before and after photolysis of caged Ca2+. Upon photolysis of caged Ca2+, fluorescence increased and then decayed to a new steady-state level within approximately 1 s, while tension increased to a new steady-state level within approximately 1.5 s. After extracting troponin C, fibers did not generate tension following the flash, but steady-state post-flash fluorescence was significantly greater than when troponin C was present. The difference in [Ca2+]free represents the amount of Ca2+ bound to troponin C. In fibers that were troponin C-replete, Ca2+ binding to troponin C did not differ at short (approximately 1.97 microm) and long (approximately 2.51 microm) sarcomere length, yet tension was approximately 50% greater at the long sarcomere length. These results show that the affinity of troponin C for Ca2+ is not altered by changes in sarcomere length, indicating that length-dependent changes in Ca2+ sensitivity of tension in skeletal muscle are not related to length-dependent changes in Ca2+ binding affinity of troponin C.

Myofibrillar calcium sensitivity of isometric tension is increased in human dilated cardiomyopathies: role of altered beta-adrenergically mediated protein phosphorylation.

To examine the role of alterations in myofibrillar function in human dilated cardiomyopathies, we determined isometric tension-calcium relations in permeabilized myocytesized myofibrillar preparations (n = 16) obtained from left ventricular biopsies from nine patients with dilated cardiomyopathy (DCM) during cardiac transplantation or left ventricular assist device implantation. Similar preparations (n = 10) were obtained from six normal hearts used for cardiac transplantation. Passive and maximal Ca2+-activated tensions were similar for the two groups. However, the calcium sensitivity of isometric tension was increased in DCM compared to nonfailing preparations ([Ca2+]50=2.46+/-0.49 microM vs 3.24+/-0.51 microM, P < 0.001). In vitro treatment with the catalytic subunit of protein kinase A (PKA) decreased calcium sensitivity of tension to a greater degree in failing than in normal preparations. Further, isometric tension-calcium relations in failing and normal myofibrillar preparations were similar after PKA treatment. These findings suggest that the increased calcium sensitivity of isometric tension in DCM may be due at least in part to a reduction of the beta-adrenergically mediated (PKA-dependent) phosphorylation of myofibrillar regulatory proteins such as troponin I and/or C-protein.

Role of atrial contraction in diastolic pressure elevation induced by rapid pacing of hypertrophied canine ventricle.

The mechanism of diastolic pressure elevation induced by acute rapid pacing in pressure-load hypertrophied left ventricles (LVs) remains incompletely understood. It has been ascribed to abnormalities of coronary flow, metabolism, and calcium cycling. However, rapid pacing also alters the timing of atrial and ventricular stimulation relative to the diastolic filling period, and this could also influence diastolic pressures. To test the role of such mechanical factors, LV pressure-volume hemodynamics were measured in closed-chested anesthetized dogs during and after abrupt cessation of rapid atrial pacing. Twenty-one dogs were studied: 6 dogs with LV hypertrophy (LVH) induced by perinephritic hypertension, 5 sham-operated normotensive dogs, and 10 acute normotensive control dogs. In LVH dogs, but not in sham-operated or control dogs, end-diastolic pressure rose progressively with increasing heart rate from 5.6 +/- 3.1 mm Hg at baseline to 22.6 +/- 8.1 mm Hg at 220 beats per minute. In all hearts, rapid pacing shifted the timing of left atrial contraction so that it occurred near the onset of LV filling rather than at end diastole. However, in LVH hearts, early LV diastolic pressure and peak atrial pressure were also markedly elevated. Most striking, immediately after terminating the pacing, diastolic pressure declined to near baseline. This rapid pressure decline occurred just when atrial systole would have ensued and before ventricular activation would have followed had pacing continued. Thus, diastolic pressure elevation resolved before a change in ventricular pacing rate. The role of atrial contraction was further explored by simultaneous atrioventricular pacing. This shifted the time of atrial systole so that it occurred during LV isovolumic contraction, while maintaining the identical LV pacing rate. This change eliminated the diastolic pressure elevation found previously. Further analysis revealed that the pressure increase during rapid pacing was not due simply to partial LV filling imposed on a relaxing ventricle or to hypertension or an intact pericardium. These data indicate that mechanical effects of atrioventricular interaction play an important role in tachycardia-induced diastolic dysfunction in this model of LVH and can be more causative than ischemia or metabolic factors in this setting.

Calcium sensitivity of isometric tension is increased in canine experimental heart failure.

To examine the role of alterations in myofibrillar function in chronic heart failure, we determined isometric tension-pCa relations in permeabilized myocardium from a canine model of dilated cardiomyopathy (DCM) produced by chronic rapid pacing. In the initial series of experiments, seven dogs were paced at 250 beats per minute for 28.9 +/- 7.0 days, resulting in ventricular dilatation and reduced ejection fractions by echocardiography and elevated intracardiac filling pressures. Isometric tension-pCa relations were measured by using mechanically disrupted and permeabilized myocyte-sized preparations obtained from left ventricular biopsies before (n = 11) and after (n = 10) chronic rapid pacing-induced heart failure. Resting sarcomere length (SL) was set at 2.35 microns, and preparations had low end compliance (SL was 2.23 +/- 0.03 microns during maximal activation). Passive tension (2.1 +/- 1.0 versus 2.4 +/- 0.6 mN/mm2) and maximal Ca(2+)-activated tension (25.9 +/- 9.3 versus 27.8 +/- 6.8 mN/mm2) were similar for control and DCM preparations, respectively. However, the calcium sensitivity of isometric tension was increased in failing myocardium (pCa50 5.95 +/- 0.11 [DCM] versus 5.83 +/- 0.10 [control], P = .001). Treatment of myofibrillar preparations with the catalytic subunit of protein kinase A decreased calcium sensitivity of tension to a greater degree in failing preparations (shift of pCa50 from 6.04 +/- 0.06 to 5.75 +/- 0.09, n = 7) than in nonfailing preparations (5.91 +/- 0.08 to 5.74 +/- 0.07, n = 8), and isometric tension-pCa relations in the two groups were not significantly different after protein kinase A treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Rate of tension development in cardiac muscle varies with level of activator calcium.

In skeletal muscle, the rate of transition from weakly bound to force-generating crossbridge states increases as calcium concentration is increased. To examine possible calcium sensitivity of this transition in cardiac muscle, we determined the kinetics of isometric tension development during steady activation in detergent-permeabilized rat ventricular trabeculae (n = 7) over a range of calcium concentrations. Force-generating crossbridges in activated trabeculae were disrupted by a brief, rapid release and restretch equivalent to 20% muscle length (15 degrees C), which resulted in a subsequent phase of tension redevelopment that was well fit by a monoexponential function (rate constant, ktr). Sarcomere length was monitored by laser diffraction and held constant during tension redevelopment by an iterative adaptive feedback control system. The ktr increased from 3.6 +/- 0.8 s-1 at the lowest calcium concentration studied (pCa 5.9) to 9.5 +/- 1.3 s-1 during maximal activation (pCa 4.5). The relationship between relative ktr and relative tension was approximately linear over a wide range of [Ca2+] (r2 = .94). This result differs quantitatively from results in skeletal muscle, in which ktr is sensitive to [Ca2+] primarily at higher activation levels. This observation is also inconsistent with a recent suggestion that the rate of force development in living myocardium is independent of the activation level. Our results in skinned myocardium can be explained by a model in which calcium is a graded regulator of both the extent and rate of binding of force-generating crossbridges to the thin filament.

Coronary angioplasty through a new 6 French guiding catheter.

Coronary angioplasty through smaller-diameter guiding catheters using predominantly fixed-wire balloon systems has been possible, but has had some limitations. The purpose of this prospective, nonrandomized study was to investigate the results of percutaneous transluminal coronary angioplasty using a new 6F guiding catheter with over-the-wire balloon systems. Coronary angioplasty using over-the-wire balloon systems through a new 6F guiding catheter was evaluated in 79 lesions in 70 patients and then compared to randomly selected procedures using 7F guiding catheters in 70 patients performed over the same time period. Coronary angioplasty through 6F guiding catheters and over-the-wire balloons including 8 long (30-mm) and 3 perfusion balloons was successful in 94.9% of lesions and in 94% of patients. Coronary angioplasty through 7F guiding catheters was successful in 97.5% of lesions and in 97.1% of patients, respectively. Success rates between 6F and 7F guiding catheter groups were similar overall and for proximal, mid, distal, or complex (total, subtotal, or length > 10-mm) lesions. There were no failures to withdraw the deflated balloon into the 6F guiding catheter. Vessel opacification after dilatation with the guidewire across the lesion was similar between the 6F and 7F guiding catheter groups. The mean change in hematocrit for the 6F procedures (-1.4 +/- 3.7%) was significantly lower than for the 7F procedures (-3.3 +/- 3.2%, P < 0.001). Coronary angioplasty using a variety of over-the-wire balloon catheters through a new 6F guiding catheter is feasible with success rates comparable to 7F guiding catheters. Angioplasty with this 6F guiding catheter reduces procedural blood loss compared to larger-lumen guiding catheters.

Diastolic compliance of hypertrophied ventricle is not acutely altered by pharmacologic agents influencing active processes.

OBJECTIVE: To test, by studying the acute effects of drugs that influence active processes, the hypothesis that in humans with marked ventricular hypertrophy, reduced chamber compliance is primarily caused by passive structural changes. DESIGN: An uncontrolled (before-after) study. SETTING: University Medical Center. PATIENTS: Fourteen patients with ventricular hypertrophy (19 +/- 4.5-mm diastolic-wall thickness) and normal resting systolic function were studied while they had invasive cardiac catheterization. INTERVENTION: Intravenous beta-blocker (esmolol) or calcium channel blocker (verapamil) or both. MEASUREMENTS: Left ventricular function was determined by pressure-volume relations. Volume was measured using conductance catheter, providing a continuous voltage signal proportional to chamber volume. Pressure was measured by micromanometer. Cardiac-specific assessment of change in chamber contractility and diastolic compliance due to each drug was determined. RESULTS: Both drugs lowered contractility by approximately 30% (P < 0.01). Esmolol slowed relaxation and reduced early peak filling rate, whereas verapamil delayed the time to peak filling (all P < 0.05). In contrast to the effects of both drugs on active contraction and early diastole, late-diastolic compliance was unaltered, and end-diastolic pressure-volume relations were almost identical. CONCLUSION: Neither beta-receptor nor calcium channel blockade acutely alters left ventricular compliance despite substantial active effects manifest in systole and early diastole. This supports the notion that chamber compliance is principally determined by passive structural elements in the heart rather than by active processes.

Brachial approach for intracoronary stent implantation: a feasibility study.

Implantation of coronary artery stents via the percutaneous femoral approach is associated with a high rate of vascular complications at the access site related to the size of the entry hole and the intense anticoagulation required to prevent stent thrombosis. Therefore we studied the feasibility of using the left brachial approach utilizing open arterial repair for implantation of coronary artery stents. Intracoronary stent implantation via the femoral approach in 24 patients (group A) was compared with implantation via the brachial approach in 16 patients (group B). Baseline lesion characteristics were similar in the two groups. All stents in group A (n = 27 stents) were successfully delivered to their target vessel. One stent in group B (n = 18 stents) could not be delivered because of an inability to engage the coronary artery from the brachial approach. There were no significant differences in the angiographic outcome between the two groups. Complications including hematomas, hemorrhage requiring blood transfusion, vascular injury requiring surgery, and pseudoaneurysm formation were significantly more common in group A than in group B (8/24 [33%] versus 1/16 [6%], respectively; p < 0.05). In addition, the length of hospital stay was significantly longer for the femoral approach than the brachial approach (9.4 vs 6.5 days, respectively; p < 0.05). Thus the left brachial approach for intracoronary stent implantation is technically feasible, safe, and associated with fewer local vascular complications and a shorter hospitalization than the femoral approach.

Coronary angioplasty using an autoperfusion balloon catheter through a 6 French guiding catheter.

Use of 6 French guiding catheters for elective percutaneous transluminal coronary angioplasty has been limited by lack of a compatible autoperfusion balloon catheter for management of complications such as acute vessel closure and large subintimal dissections. We describe the successful use of a lower profile autoperfusion balloon catheter through large internal lumen 6F guiding catheters for elective coronary angioplasty. These cases demonstrate the feasibility of the use of autoperfusion balloon catheters with 6F guiding catheters in elective, and presumably also in emergent, settings.

Percutaneous transluminal coronary angioplasty through 6F diagnostic catheters: a feasibility study.

This study evaluated the feasibility of performing coronary angioplasty through 6F diagnostic catheters by mainly using over-the-wire balloon systems on 84 lesions in 70 patients. Procedural variables, including vessel opacification and angioplasty outcome, were assessed. Changes in hematocrit after angioplasty were compared for 6F versus 7F and 8F systems. Successful 6F dilatation was performed in 72 (85.7%) of 84 lesions and 58 (82.9%) of 70 patients. Seven of the 12 lesions unable to be dilated with 6F systems were successfully dilated with larger French systems. Coronary artery opacification with the 6F catheters after balloon dilation was less than optimal with the balloon and guidewire still in the catheter. Changes in hematocrit after 6F procedures were significantly less than for 8F procedures (-2.1% vs -4.2%, respectively, p < 0.01) but not for 7F procedures (-2.4%, p = not significant). Potential cost savings for angioplasty with 6F diagnostic catheters could be significant. Thus angioplasty with over-the-wire balloon systems in which 6F nontapered diagnostic catheters are used can be performed safely and with less procedural blood loss than with 8F systems. Significant problems encountered with the current catheter design were poor vessel opacification after balloon dilation and difficulties with balloon retraction.

Preprocedural anticoagulation does not reduce angioplasty heparin requirements.

To determine whether continuous preprocedural heparin influences the need for anticoagulation during percutaneous transluminal coronary angioplasty (PTCA), we compared heparin requirements in patients therapeutically anticoagulated after continuous heparinization for > or = 12 hours with patients not pretreated with heparin (controls). A Hemochron device was used to monitor the activated clotting time (ACT) values during the procedure. An ACT > or = 300 seconds was used as a measure of optimal anticoagulation. Patients pretreated with heparin had significantly higher preprocedural ACT measurements (163 +/- 31.5 vs 126 +/- 13 seconds, p < 0.001) and partial thromboplastin time (PTT) measurements (46 +/- 15 vs 25 +/- 3 seconds, p < 0.001) than controls. While the amount of heparin needed to achieve an initial ACT > 300 seconds was slightly greater in control patients (10,682 +/- 1,852 vs 9,269 +/- 2,993 units, p < 0.001), the total heparin required to maintain an ACT > 300 seconds throughout the procedure was similar between the two groups (11,551 +/- 3,181 units vs 12,136 +/- 2,575 units, p = NS). Thus preprocedural anticoagulation does not significantly reduce total heparin requirements, and these patients should receive the same initial heparin regimen as patients not pretreated with intravenous heparin.

Coronary artery rupture and pseudoaneurysm formation resulting from percutaneous coronary angioscopy.

We describe a case in which coronary angioscopy was complicated by inability to deflate the device's occlusion balloon. Rapid over-inflation to rupture the balloon resulted in massive dissection of the artery, pseudoaneurysm formation, and ultimately coronary bypass. While the cause of failure of balloon deflation remains obscure, deliberate over-inflation to cause rupture may be hazardous.

Alterations in left ventricular mechanics, energetics, and contractile reserve in experimental heart failure.

The contributions of changes in primary systolic and diastolic properties, limitations of contractile reserve, and alterations in energy efficiency to the left ventricular dysfunction seen with chronic pacing tachycardia were investigated. Seven dogs (heart failure group) were ventricularly paced at 250 beats per minute for 26.3 +/- 2.9 days and compared with a separate control group (n = 8). STudies were performed with isolated, metabolically supported hearts coupled to a computer-controlled loading system. Pressure-volume relations and myocardial oxygen consumption (MVO2) were measured to assess chamber systolic and diastolic properties and efficiency (relation between MVO2 and pressure-volume area [PVA]). Systolic function was reduced in failure hearts versus controls as assessed by the slope of the end-systolic pressure-volume relation (1.29 +/- 0.94 versus 2.71 +/- 0.98 mm Hg/ml, p less than 0.01) and lowered end-systolic stiffness at a matched stress (956.1 +/- 123.5 versus 1,401.7 +/- 431.7 g/cm2, p less than 0.05). Diastolic chamber and myocardial stiffness were unaltered in failure hearts, but the unstressed diastolic-arrested volume was significantly larger (33.3 +/- 3.9 versus 21.9 +/- 7.6 ml, p less than 0.01). Inotropic response to increased heart rate and exogenous beta-adrenergic stimulation (dobutamine HCl) was significantly impaired in failure compared with control hearts. Most interestingly, failure hearts had a lowered slope of the MVO2-PVA relation (2.1 +/- 1.1 versus 2.9 +/- 1.4 ml O2.mm Hg-1.ml-1.100 g left ventricle-1, p less than 0.001), indicating increased efficiency of chemomechanical energy conversion. The y intercept of the MVO2-PVA relation, which reflects oxygen costs of basal metabolism and excitation-contraction coupling, was unchanged in the two groups despite decreased contractility of the heart failure hearts. These results demonstrate reduced chamber and myocardial contractility, dilatation without alteration of passive myocardial properties, impaired contractile reserve, and novel alterations in cardiac efficiency in this model of heart failure.