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PubMed1994

Dramatic improvement of severe dilated cardiomyopathy in an acromegalic patient after treatment with octreotide and trans-sphenoidal surgery.

Severe congestive heart failure developed in an acromegalic patient, and was successfully treated with octreotide followed by trans-sphenoidal surgery. Clinical, hormonal echocardiographic and haemodynamic findings as well as histological heart examination before and after treatment revealed that over-production of growth hormone may induce the myocardial cell degeneration responsible for mechanical heart dysfunction. In addition, this unique example demonstrates the reversibility of myocardial damage following octreotide and trans-sphenoidal surgery, leading to significant improvement in cardiac function with minimal diastolic dysfunction and moderate interstitial fibrosis.

Acromegaly↗
PubMedDate not supplied

[Clinical and developmental aspects of cardiac involvement in infant of diabetic mother].

The authors evaluated the main clinical and evolutive aspects of heart involvement in the newborn of diabetic mother (IDM). We studied the files of 35 IDM in a 4 years period; they were investigated the first week of life and at 6-12 months (18 cases). Most of the patients were asymptomatic/signs of extracardiac suffering; 15 had a systolic murmur. ECG: left ventricle (LV) hypertrophy (8) and LV repolarization disturbances (19 cases). Chest X-ray: cardiomegaly (9 cases). Echocardiography: hypertrophic cardiomyopathy (HCM), especially septal (25 cases, 71%); LV diastolic dysfunction (19-35) and normal systolic function; pulmonary hypertension (3), other congenital heart diseases (8 cases). The control revealed the alleviation of the LV walls size and LV diastolic function. The high incidence of the cardiac manifestations in IDM and the risk of occurrence of some severe problems, require a complete cardiological exam from the first few days of life and a follow-up schedule until the normalization of the cardiac parameters.

Adult↗
PubMed1993

[Prolonged diastolic stunning after unstable anginal attacks].

To evaluate the changes in the left ventricular diastolic filling dynamics after severe myocardial ischemia, serial pulsed Doppler examinations of mitral flow were performed in 10 patients with unstable angina. Peak early and late filling velocities (E and A), the ratio (E/A), the area E (Ei) and A (Ai) and the ratio (Ei/Ai) were measured one, 3, and 7 days and one month after the last ischemic episode. Seven of 10 patients were treated with percutaneous transluminal coronary angioplasty (PTCA), and the same indexes were obtained one, 3, and 7 days and one month after PTCA. E/A and Ei/Ai increased significantly on the 3rd and 7th days, however, no further increase was observed one month after the last ischemic episode and after PTCA. Left ventricular diastolic dysfunction induced by severe myocardial ischemia persisted for several days after the stabilization of myocardial ischemia. After the ischemic episodes were stabilized by administering pharmacological therapy, left ventricular diastolic dynamics were unchanged before and after PTCA. These results indicate that there may be diastolic myocardial stunning in patients with unstable angina.

Angina, Unstable↗
PubMed1998

[Management of chronic heart failure].

Throughout the last years the concept and methods of treatment of chronic heart failure have considerably changed. The objective of the treatment is not only the relief of the symptoms, but also prevention of the onset and progression of the disease. The emphasis of treatment aims to moderate the increased neuroendocrine activity and thus to prevent myocardial damage. This review summarizes our knowledge concerning the treatment of chronic heart failure due to left ventricular dysfunction. It is based on former American guidelines and especially on the guideline of the Task Force of the European Society of Cardiology. The treatment of systolic and diastolic dysfunction of left ventricle are separately discussed. Emphasis is laid on the non pharmacologic treatment of heart failure. The treatment with ACE-inhibitors, diuretics, betablockers, digitalis, calcium antagonists and other drugs as well as the invasive procedures are also discussed.

Adrenergic beta-Antagonists↗
PubMed2001

[Aspects of diastolic function of the heart in vibration disease].

AIM: To study effects of occupational vibrations on the myocardium, to elucidate early alterations in cardiac performance and to introduce approaches to their correction. MATERIALS AND METHODS: Doppler echocardiography was made to evaluate diastolic function of the heart ventricles in 54 men with vibration disease. Mean exposure to local vibration was 22.4 years. The examinees were divided into two groups: 42 men (mean age 46.8 years) with vibration disease of the first degree--group 1; 12 men (mean age 51.2 years) of the first-second and second degree--group 2. RESULTS: In group 2 compared to group 1 there was a decrease of maximal velocity of early filling (MVEF) by 24.2%, early filling phase (EFP) by 27%, ratio MVEF/MVLF 1.17-fold, increase of isometric relation phase by 15.9%. For the right ventricle there was a decrease in MVEF by 15.4%, MVEF/MVLF 1.51-fold, prolongation of EFP by 20%. By these indices, the groups differed significantly in the diseases severity. Trimetasidine had a corrective effect on diastolic function of both left and right ventricles of the heart. CONCLUSION: Patients with vibration disease were diagnosed to have left and right ventricular diastolic dysfunction.

Data Interpretation, Statistical↗
PubMed2000

Diastolic biomechanics in normal infants utilizing MRI tissue tagging.

BACKGROUND: Most of what is known about diastolic function in normal infants is derived from flow and pressure measurements. Little is known about regional diastolic strain and wall motion. METHODS AND RESULTS: Magnetic resonance tissue tagging was performed in 11 normal infants to determine regional diastolic strain and wall motion. Tracking diastolic motion of the intersection points and finite strain analysis yielded regional rotation, radial displacement, and E(1) and E(2) strains at 3 short-axis levels (significance was defined as P<0.05). E(2) "circumferential lengthening" strains were significantly greater at the lateral wall, regardless of short-axis level, whereas E(1) "radial thinning" strains were similar in all wall regions at all short-axis levels. In general, no differences were noted in strain dispersion within a wall region or in endocardial/epicardial strain at all short-axis levels. At all short-axis levels, septal radial motion was significantly less than in other wall regions. No significant differences in radial wall motion between short-axis levels were noted. Rotation was significantly greater at the apical short-axis level in all wall regions than in other short-axis levels, and it was clockwise. At the atrioventricular valve, septal and anterior walls rotated slightly clockwise, whereas the lateral and inferior walls rotated counterclockwise. CONCLUSIONS: Diastolic biomechanics in infants are not homogeneous. The lateral walls are affected most by strain, and the septal walls undergo the least radial wall motion. Apical walls undergo the most rotation. These normal data may help in the understanding of diastolic dysfunction in infants with congenital heart disease.

Biomechanical Phenomena↗
PubMed2001

An angiotensin-converting enzyme inhibitor improves left ventricular systolic and diastolic function in transfusion-dependent patients with beta-thalassemia major.

BACKGROUND: Cardiac complications are the major cause of death in patients with beta-thalassemia major. The purpose of this study was to assess the impact of long-term treatment with the angiotensin-converting enzyme inhibitor enalapril on left ventricular (LV) performance, with an emphasis on diastolic LV function because diastolic dysfunction has been found to be an early event in an asymptomatic thalassemic population with only mild impairment of LV systolic function. METHODS: We used echocardiography to study the impact of treatment with oral enalapril on the evolution of standard M-mode and Doppler indices, along with a recently introduced Doppler index of combined systolic and diastolic LV performance. RESULTS: Patients were found to have significantly increased LV end-diastolic dimensions (LVEDD), LV end-systolic dimensions (LVESD), and left atrial dimensions and decreased LV fractional shortening (LVFS) compared with controls. After treatment with enalapril, LVESD decreased from 3.58 +/- 0.3 cm to 3.23 +/- 0.4 cm (P <.01) and LVFS increased from 32.6% +/- 4.0% to 38.0% +/- 3.1% (P <.001). Patients at baseline were found to have a significantly higher E-wave velocity, E/A ratio, and Doppler index compared with controls. The E-wave deceleration time was significantly shorter compared with that of controls. After treatment with enalapril, the E/A ratio decreased from 2.10 +/- 0.42 to 1.50 +/- 0.30 (P <.05), E-wave deceleration time increased from 0.12 +/- 0.02 seconds to 0.15 +/- 0.03 seconds (P <.01), and the Doppler index decreased from 0.46 +/- 0.10 to 0.37 +/- 0.14 (P <.05). CONCLUSIONS: Enalapril was well tolerated in asymptomatic or minimally symptomatic patients with LV dysfunction resulting from beta-thalassemia major. Echocardiographically we demonstrated significant improvement in LV systolic and diastolic function. Whether this translates to improved long-term prognosis and survival remains to be further evaluated.

Adult↗
PubMed1988

Diastolic abnormalities in young asymptomatic diabetic patients assessed by pulsed Doppler echocardiography.

Indexes of left ventricular diastolic filling were measured by pulsed Doppler echocardiography in 21 insulin-dependent diabetic patients and 21 control subjects without clinical evidence of heart disease. No patient had chest pain or electrocardiographic changes during exercise testing. The mean age of patients was 32 years. All patients had a normal ejection fraction. Six (29%) of the 21 diabetic patients had evidence of diastolic dysfunction as assessed by the presence of at least two abnormal variables of mitral inflow velocity. The ratio of peak early to peak late (atrial) filling velocity was significantly decreased in diabetic compared with control subjects (1.24 +/- 0.21 versus 1.66 +/- 0.30, p. less than 0.001). Atrial filling velocity was significantly increased in diabetic patients (74.3 +/- 16.7 versus 60.3 +/- 12.2 cm/s, p less than 0.004), whereas early filling velocity was reduced by a nearly significant degree (88.8 +/- 12.6 versus 98.5 +/- 18.8 cm/s, p less than 0.057). The atrial contribution to stroke volume as assessed by area under the late diastolic filling envelope compared to total diastolic area was also significantly increased in diabetic compared with control subjects (35 versus 27%, p less than 0.001). Left ventricular diastolic filling abnormalities in diabetic patients did not correlate with duration of diabetes, retinopathy, nephropathy or peripheral neuropathy. These data suggest that approximately one-third of such patients have subclinical myocardial dysfunction unrelated to accelerated atherosclerosis. Doppler echocardiography may offer a reliable noninvasive means to assess diastolic function and to follow up diabetic patients serially for any deterioration in cardiac status before the appearance of clinical symptoms.

Adult↗
PubMed2006

[Effect of high-dose chemotherapy with subsequent transplantation of blood-forming cells on left ventricle function in patients with malignant lymphomas treated with doxorubicin in primary chemotherapy].

PURPOSE OF STUDY: The authors examined whether high-dose chemotherapy with hematogenic tissue transplantation might negatively affect function of left ventricle (LV) in oncology patients with malignant lymphomas initially treated with conventional chemotherapy consisting of doxorubicin (DOX) in contrast to patients treated without the transplantation in medium-term follow up. PATIENTS AND METHODOLOGY: The follow up group included 77 patients (39 women/38 men) at the age of 36 +/- 15 (median 30, 16-67 years). All 77 patients were treated with initial chemotherapy with DOX, 22 out of that group later received high-dose chemotherapy with hematogenic tissue transplantation (HTT). 16 (73 %) patients of this subgroup underwent autologous transplantation and 5 (23 %) allogeneic transplantation. One female patient (4 %) underwent both autologous and allogeneic transplantation. The follow up period after completion of initial chemotherapy was 5-10 years (median 6 years). The patients were examined with rest echocardiography before start, after chemotherapy, and during follow-up examination. Spiroergometric test (SET) was only performed at the follow-up examination. RESULTS: Both subgroups showed significant decrease of ejection fraction (EF) after chemotherapy, with further decrease in the control examination period, without mutual difference. While the HTT (HTT+) group showed no EF drop below 50 %, in the non-HTT (HTT-) group EF dropped in two (4 %) patients after chemotherapy and in four (8%) patients at the control examination. Progressing decrease of EF > 10 % was reported with 25 % of the HTT- patients (p < 0.05), but with just 13 % of the HTT+ patients (non-significant). The diastolic insufficiency (DF) was present identically in both groups with 36 % of the patients, which represents a statistically significant increase in comparison to the pre-chemotherapy condition. SET did not show any differences in burden toleration and circulation indicators between the two groups. The drop of pVO2 < 20 ml/kg/min occurred with 22 patients of both groups. Linear regression data analysis revealed existence of a significant relationship between EF change, some diastolic function indicators, pVO2 and cumulative dose of DOX (p < 0.05). The current age significantly and negatively correlated with pVO2 (p < 0.001) and DF indicators (p < 0.001). The follow up period inversely correlates with the changes of EF (p < 0.05) and pVO2 (p < 0.05), not correlating with diastolic function indicators. Multi-variant analysis did not confirm any higher risk of administration of high-dose chemotherapy with HTT for significant drop of EF or its drop down to the pathological zone below 50 % (OR = 0.46; non-significant), for discovery of reduced cardio-pulmonary performance (pVO2 < 20 ml/kg/min) (OR = 0.35; non-significant) or for development of diastolic dysfunction (OR = 1.0; non-significant). CONCLUSIONS: Treatment with high-dose chemotherapy with HTT application within medium-term follow up does not result in any significant systolic or diastolic malfunction of myocardium and deterioration of cardiopulmonary performance in comparison to patients not undergoing this therapy. Treatment with cardiotoxic doxorubicin administered in the context of basic conventional chemotherapy is most likely to be responsible for occurrence of the pathological effects across the followed up group. Length of monitoring is a significant factor correlating with changed ejection fraction. This finding justifies the need for long-term prospective monitoring of ejection fraction of the left ventricle in adult patients treated with cardiotoxic chemotherapy.

Adolescent↗
PubMed1991

Left ventricular diastolic filling in patients with coronary artery disease without myocardial infarction.

Left ventricular diastolic dysfunction at rest was studied in 24 patients with coronary artery disease but no evidence of previous myocardial infarction. Seven patients with normal coronary arteries were studied as control. Diastolic filling was analyzed by the serial left ventricular volume and 14 radial axes from the gravity point of the left ventricle with cine left ventriculography. There were no differences in the systolic function between coronary artery disease and the normal control. Peak filling rate was decreased significantly in the groups with left anterior descending artery disease (LAD, p less than 0.05) and multivessel disease (MVD, p less than 0.05), but not in the group with right coronary artery disease (RCA). Time to peak filling rate was prolonged in each group of LAD (p less than 0.05), RCA (p less than 0.05), and MVD (p less than 0.001), compared with controls. The time-volume curve showed disturbed rapid filling in the LAD and RCA groups, and also both depressed rapid and slow filling in the MVD group. In the LAD group, the filling fraction was decreased significantly at the time of 25% of the diastolic period (p less than 0.001) and radial distension to the anterior wall was decreased at the time of 25%, 50%, and 75% of the diastolic period, compared with controls. In the RCA group, the filling fraction (p less than 0.001) and radial distension to the posterior wall were decreased only at the time of 25% of the diastolic period. In the MVD group, filling fraction and radial distension to the most wall were decreased at 25%, 50%, and 75% of the diastolic period.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2000

New Doppler echocardiographic applications for the evaluation of early alterations in left ventricular diastolic function after coronary angioplasty.

AIMS: The early effect of percutaneous transluminal coronary angioplasty on left ventricular diastolic dysfunction was investigated with the aid of new Doppler echocardiographic applications. METHODS: Thirty patients with isolated severe left anterior descending coronary artery stenosis were included. All patients exhibited abnormal diastolic function demonstrated by prolonged isovolumic relaxation and deceleration time and decreased E/A ratio. New Doppler indexes included the flow propagation velocity of E wave, E and A waves' transit time to the left ventricular outflow tract, the ratio of these transit times in addition to the traditional isovolumic relaxation time, mitral deceleration time, and early and late transmitral peak flow velocities. All measurements were performed within 4 h before angioplasty and repeated within 24 h after the procedure. RESULTS: After angioplasty none of these parameters, except the A-wave transit time, were changed significantly. The A-wave transit time increased significantly from 57 +/- 5 ms to 78 +/- 7 ms within 24 h after successful angioplasty. The ratio of E- and A-wave transit time decreased significantly due to this significant increase in A-wave transit time. CONCLUSION: In this study, early improvement of Doppler index of left ventricular diastolic compliance is demonstrated after successful angioplasty.

Adult↗
PubMed1991

[Radionuclide ventriculography in the evaluation of the diastolic function of the left heart ventricle].

A maximum filling rate (FRmax), the time of reaching it (T-FRmax), the fraction of filling of the first and second diastolic thirds (FF1/3 and FF2/3), an increment of the volume in the first and second diastolic thirds (delta V1 and delta V2) were investigated on the basis of radionuclide ventriculography findings, 99mTc being used. CHD patients (n = 133) were characterized by a decrease in FF1/3, FRmax, an increase in T-FRmax changes in the ratio of delta V1 and delta V. A normal filling process was characterized by predominance of filling in the first diastolic third (the fast filling phase - delta V1 greater than greater than delta V2). Left ventricular diastolic dysfunction was characterized either by a homogeneous distribution of filling in the phase of fast or slow filling with practically equal increasing of volumes in the first and second diastolic thirds (delta V1 = delta V2) or by shifted filling during diastasis (delta V1 less than delta V2).

Coronary Disease↗
PubMed1987

10-year results and survival of patients with hypertrophic cardiomyopathy treated with calcium antagonists.

Hypertrophic cardiomyopathy is characterized by progredient myocardial hypertrophy causing ventricular systolic and diastolic dysfunction. Long-term results of beta-blocker therapy have been disappointing. Neither the impaired ventricular filling or the prognosis are improved. In contrast, calcium antagonists mainly influence diastolic ventricular dynamics, but also have beneficial effects on systolic function. The results of long-term therapy with calcium antagonists, including patients treated for more than 10 years, are presented here. A total of 84 consecutive patients (mean age 43 years; 20 female and 64 male) with confirmed hypertrophic cardiomyopathy were treated with high doses of calcium antagonists (mean doses of 515 mg verapamil or 158 mg gallopamil per day). In the course of therapy with a mean duration of 52 months, heart size--assessed by X-ray technique--and Sokolow-index in the ECG decreased significantly (heart volume: from 947 to 885 ml/1.73 m2 body surface; Sokolow-index: from 5.0 to 4.5 mV). The echocardiogram showed a significant decrease in left atrial diameter, whereas wall thickness only tended to decrease. Hemodynamic control investigations confirmed an improvement in systolic as well as in diastolic ventricular function (mean follow-up period was 31 months). According to these findings the condition and stress tolerance improved in 84% of the patients. Therapy with calcium antagonists also improved prognosis: without treatment or following treatment with beta-blocking agents, annual mortality is approximately 3.5%, whereas in the described patient population mortality dropped to less than 2%. Thus, a calcium antagonist is the medication of first choice for patients with hypertrophic cardiomyopathy.

Adolescent↗
PubMed2004

Left ventricular hypertrophy differences in male professional runners and in young patients suffering from mild hypertension.

AIMS: This study was executed to evaluate left ventricular (LV) geometry, diastolic and systolic function assessed by B- and M-mode and pulsed Doppler echocardiography in a group of professional sprinter runners (group I), in young patients suffering from mild hypertension (group II) and in control young adults (group III). Twenty-one male sprinter runners were checked during a period of training and compared with 19 young patients suffering from mild hypertension and 15 healthy controls matched for gender and body size. FINDINGS: LV septum thickness, LV posterior wall thickness, LV ejection fraction, LV shortening fraction, midwall fractional shortening and stroke volume were significantly higher in runners compared to hypertensive patients and controls (p < 0.001). A significant increase of diastolic function parameters of the early peak flow velocity, E, and the early/late diastolic wave ratio, E/A, and in the isovolumic relaxation time or in the E velocity deceleration time wave was observed in hypertensive patients when compared to runners and controls (p < 0.05). The study of the pulmonary venous flow revealed a significant increase in the early systolic flow velocity, S, in hypertensive patients compared to runners (p < 0.05); the late diastolic flow velocity, D, appeared to be similar in all groups, while atrial backward flow velocity, Ar, was higher in group I and II respect to control (p < 0.001). CONCLUSIONS: Our data indicate that LV concentric hypertrophy in sportsmen is associated with improvement of systolic and diastolic performance, whereas diastolic dysfunction can occurs even in the early stages of hypertension in young patients, in whom an alteration in the LV filling appears even in absence of systolic dysfunction and evident concentric myocardial hypertrophy.

Adaptation, Physiological↗
PubMed2005

Assessment of left ventricular diastolic function by Doppler tissue imaging in children with end-stage renal disease.

AIM: To evaluate left ventricular (LV) diastolic function in children with end-stage renal disease (ESRD) using conventional pulsed-Doppler echocardiography and Doppler tissue imaging (DTI), and to compare the findings with these two modalities. METHODS: Twenty-four children with ESRD and 22 healthy age- and sex-matched control subjects were assessed with conventional Doppler echocardiography and DTI. The scans of the renal disease patients were done after a dialysis session. Parameters related to LV systolic and diastolic function were compared in the ESRD and control groups. RESULTS: The ESRD patients had lower mean mitral E/A ratio both according to conventional Doppler echocardiography and TDI than the control subjects. The ESRD group also had significantly longer isovolumetric relaxation time (116+/-31 ms vs 97+/-3.1 ms, respectively; p<0.001), and significantly longer deceleration time (235+/-44 ms vs 202+/-35 ms, respectively; p<0.01) than the control group. CONCLUSION: DTI findings correlate well with conventional Doppler echocardiography findings. Children with ESRD show, after dialysis, echocardiographic signs of LV diastolic dysfunction.

Adolescent↗
PubMedDate not supplied

Matrix, cytoskeleton, or myofilaments: which one to blame for diastolic left ventricular dysfunction?

During cardiac filling, the relative contribution of distension of interstitial collagen, of distension of cytoskeletal proteins, and of low-grade diastolic cross-bridge cycling in the generation of diastolic left ventricular (LV) pressure remains unclear. In failing myocardium, interstitial collagen deposition and cross-linking are augmented. This increase in collagen deposition is accompanied by expression of a stiffer isoform of titin in the cardiomyocytes. Higher diastolic stiffness of failing myocardium is therefore not necessarily related to increased interstitial collagen content. Moreover, phosporylation of titin by protein kinase A and G, and inhibition of titin-actin interaction by cytosolic calcium allow for dynamic modulation of its diastolic tension generation and could account for acute shifts of myocardial distensibility. Acute shifts of myocardial distensibility, as occur in hypertrophy or in demand ischemia, have usually been attributed to a diastolic resurgence of cross-bridge interaction. In hypertrophied and failing myocardium, the recent demonstrations of diastolic calcium release from the ryanodine receptor, of deficient diastolic calcium removal from the cytosol, and of enhanced myofilamentary calcium sensitivity support residual diastolic cross-bridge interaction. In demand ischemia, the role of calcium overload in the reduction of diastolic LV distensibility is less clear because of correction of the reduced diastolic LV distensibility by quick stretches but not by a calcium desensitizer. Simultaneous imposition in animal models of multiple molecular changes involving interstitial, cytoskeletal, and myofilamentary proteins could elucidate their relative importance for myocardial stiffness and lead to selective correction of diastolic LV dysfunction as a novel mode of heart-failure therapy.

Actin Cytoskeleton↗
PubMed1999

Echocardiographic characterization of left ventricular diastolic properties in patients presenting for the maze procedure.

The aim of this study is to characterize and compare the left ventricular (LV) diastolic filling patterns in patients with paroxysmal (PAF) versus chronic atrial fibrillation (CAF) undergoing the maze procedure and to examine their relation with the hemodynamic status. Fifty patients with PAF and 22 with CAF were studied. Hemodynamic measurements and transesophageal echocardiography (TEE) were performed after the induction of anesthesia but before surgical incision, at stable conditions. Transmitral (TMF) and pulmonary venous flow (PVF) velocities were recorded with the pulsed Doppler method. Statistical analysis between the two groups (PAF and CAF) was performed using Student's t-test and chi-squared test, with P less than .05 statistically significant. Compared with patients in the PAF group, those in the CAF group had: (1) higher pulmonary capillary wedge pressure (14 +/- 5 v 12 +/- 4 mm Hg; P < .05), (2) lower left ventricular fraction of area change (43% +/- 6% v 52% +/- 9%; P < .01), (3) slower PVF systolic wave velocity (23 +/- 10 v 35 +/- 15 cm/s; P < .05), and (4) lower ratio of PVF systolic to diastolic wave velocity (0.75 +/- 0.3 v 1.2 +/- 0.4; P < .05). In the present study, LV filling patterns of abnormal relaxation were found in all our patients who underwent the maze procedure for CAF or PAF. Although the cause of LV filling abnormalities is not apparent, the data suggest LV diastolic dysfunction is prevalent in these patients.

Adult↗
PubMed1996

Polymyxin B, a protein kinase C inhibitor, abolishes preconditioning-induced protection against contractile dysfunction in the isolated blood perfused rat heart.

The aims of this study were (1) to determine the characteristics of preconditioning against contractile dysfunction in a blood perfused isolated heart model in the presence of a physiologic combination of substrates, and (2) to determine if protein kinase C (PKC) is involved in preconditioning in this model. In order to investigate these aims, isolated isovolumic, blood perfused rat hearts (balloon-in-LV, n = 6/group) were perfused normoxically for 30 min and then divided into three groups and subjected to: (1) a further 30 min of perfusion (control group) (2) a further 20 min of perfusion + 5 min of ischaemia and 5 min of reperfusion (1 x preconditioned group) and (3) 3 x (5 min of ischaemia+5 min of reperfusion) (3 x preconditioned group). All hearts were then subjected to 30 min of ischaemia and 30 min of reperfusion. Contractile function, myocardial oxygen consumption (MVO2), lactate release and creatine kinase release were all assessed. To determine if PKC is involved in the mechanism of preconditioning in this model, the control and 3 x preconditioned group experiments were repeated in the presence of polymyxin B (50 microM), a relatively specific PKC inhibitor. Final recovery of LVDP was 31 +/- 12, 67 +/- 6 and 60 +/- 5% in the control, 1 x and 3 x preconditioned groups, respectively. Protection of contractile function was accompanied by both a preservation of diastolic function and the ratio of MVO2 to contractile function (ratio of metabolic:mechanical efficiency). However, lactate release was decreased only in the 3 x preconditioned group. Polymyxin B abolished preconditioning-induced protection against contractile and diastolic dysfunction and the protection of the ratio of MVO2 to contractile function. Lactate release was still however reduced in the polymyxin B-preconditioned group. Thus, preconditioning-induced protection against contractile dysfunction appears to be accompanied by a preservation of both diastolic function and the metabolic: mechanical efficiency and is effective in the presence of a physiologic combination of substrates. However, limitation of glycolysis during ischaemia, as assessed by lactate release, appears to be an epiphenomenon of the preconditioning protocol and is not consistently related to protection. PKC activation appears to be pivotal to the mechanism of protection against contractile dysfunction, since administration of polymyxin B abolished any protection.

Animals↗