Correlation of contractile dysfunction and abnormal tissue energy metabolism during hypoperfusion with norepinephrine in isolated rat hearts: Differences between normal and diabetic hearts

Higuchi, Makie; Ikema, Shoko; Sakanashi, Matao

doi:10.1016/0022-2828(92)93177-l

Cited by 9 publications

(4 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have shown that hearts from diabetic rats are equally [22] or more [5,23] sensitive to ischemic injury. In contrast, previous reports have demonstrated that glucose supply plays a critical cardioprotective role in cardiac responses during acute ischemia.…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia can delay left ventricular dysfunction but not autonomic damage after myocardial infarction in rodents

Rodrigues

Rosa

Medeiros

et al. 2011

Cardiovasc Diabetol

View full text Add to dashboard Cite

BackgroundAlthough clinical diabetes mellitus is obviously a high risk factor for myocardial infarction (MI), in experimental studies disagreement exists about the sensitivity to ischemic injury of an infarcted myocardium. Recently, our group demonstrated that diabetic animals presented better cardiac function recovery and cellular resistance to ischemic injury than nondiabetics. In the present study, we evaluated the chronic effects of MI on left ventricular (LV) and autonomic functions in streptozotocin (STZ) diabetic rats.MethodsMale Wistar rats were divided into 4 groups: control (C, n = 15), diabetes (D, n = 16), MI (I, n = 21), and diabetes + MI (DI, n = 30). MI was induced 15 days after diabetes (STZ) induction. Ninety days after MI, LV and autonomic functions were evaluated (8 animals each group). Left ventricular homogenates were analyzed by Western blotting to evaluate the expression of calcium handling proteins.ResultsMI area was similar in infarcted groups (~43%). Ejection fraction and +dP/dt were reduced in I compared with DI. End-diastolic pressure was additionally increased in I compared with DI. Compared with DI, I had increased Na+-Ca2+ exchange and phospholamban expression (164%) and decreased phosphorylated phospholamban at serine16 (65%) and threonine17 (70%) expression. Nevertheless, diabetic groups had greater autonomic dysfunction, observed by baroreflex sensitivity and pulse interval variability reductions. Consequently, the mortality rate was increased in DI compared with I, D, and C groups.ConclusionsLV dysfunction in diabetic animals was attenuated after 90 days of myocardial infarction and was associated with a better profile of calcium handling proteins. However, this positive adaptation was not able to reduce the mortality rate of DI animals, suggesting that autonomic dysfunction is associated with increased mortality in this group. Therefore, it is possible that the better cardiac function has been transitory, and the autonomic dysfunction, more prominent in diabetic group, may lead, in the future, to the cardiovascular damage.

show abstract

Section: Discussionmentioning

confidence: 99%

Hyperglycemia can delay left ventricular dysfunction but not autonomic damage after myocardial infarction in rodents

Rodrigues

Rosa

Medeiros

et al. 2011

Cardiovasc Diabetol

View full text Add to dashboard Cite

show abstract

“…The changes in cardiac mechanical parameters correlate with decreased ATP and increased lactate in the inner layer of the left ventricle in diabetic rats. But, of course, this cannot be explained by the rate of decrease in total ATP and lactate accumulation alone [50]. Recent evidence implicates disturbances in cardiac energy metabolism; in the uncontrolled diabetic state, cardiac myocytes use fatty acids almost exclusively to support ATP synthesis [51].…”

Section: Experimental Diabetes-induced Cardiovascular Complicationsmentioning

confidence: 99%

Glycoxidative Stress and Cardiovascular Complications in Experimentally-Induced Diabetes: Effects of Antioxidant Treatment

Karasu¹

2010

TOCMJ

View full text Add to dashboard Cite

Diabetes mellitus (DM) is a common metabolic disease, representing a serious risk factor for the development of cardiovascular complications, such as coronary heart disease, peripheral arterial disease and hypertension. Oxidative stress (OS), a feature of DM, is defined as an increase in the steady-state levels of reactive oxygen species (ROS) and may occur as a result of increased free radical generation and/or decreased anti-oxidant defense mechanisms. Increasing evidence indicates that hyperglycemia is the initiating cause of the tissue damage in DM, either through repeated acute changes in cellular glucose metabolism, or through long-term accumulation of glycated biomolecules and advanced glycation end products (AGEs). AGEs are formed by the Maillard process, a non-enzymatic reaction between ketone group of the glucose molecule or aldehydes and the amino groups of proteins that contributes to the aging of proteins and to the pathological complications of DM. In the presence of uncontrolled hyperglycemia, the increased formation of AGEs and lipid peroxidation products exacerbate intracellular OS and results in a loss of molecular integrity, disruption in cellular signaling and homeostasis, followed by inflammation and tissue injury such as endothelium dysfunction, arterial stiffening and microvascular complications. In addition to increased AGE production, there is also evidence of multiple pathways elevating ROS generation in DM, including; enhanced glucose auto-oxidation, increased mitochondrial superoxide production, protein kinase C-dependent activation of NADPH oxidase, uncoupled endothelial nitric oxide synthase (eNOS) activity, increased substrate flux through the polyol pathway and stimulation of eicosanoid metabolism. It is, therefore, not surprising that the correction of these variables can result in amelioration of diabetic cardiovascular abnormalities. A linking element between these phenomena is cellular redox imbalance due to glycoxidative stress (GOS). Thus, recent interest has focused on strategies to prevent, reverse or retard GOS in order to modify the natural history of diabetic cardiovascular abnormalities. This review will discuss the links between GOS and diabetes-induced cardiovascular disorders and the effect of antioxidant therapy on altering the development of cardiovascular complications in diabetic animal models.

show abstract

“…BMIPP uptake was also correlated with ATP concentration [4]. In rats, the ATP content of the diabetic heart was decreased [13]; such a heart was more susceptible to depletion of ATP and more likely to experi ence increased left ventricular stiffness [14], Additionally, high concentrations of fatty acids depressed functional recovery of the diabetic heart when they were present dur ing ischemia [ 15]. Our results, in which postischemic ven tricles in diabetic patients revealed a discordant decrease in BMIPP uptake, as compared with those in nondiabetic patients, may be explained by a metabolic derangement in the diabetic myocardium.…”

Section: Diabetes With Chdmentioning

confidence: 91%

Myocardial Uptake of an lodinated Branched Fatty Acid Analog, Assessed by SPECT, May Detect Metabolic Derangement of the Myocardium in Diabetic Patients with Coronary Heart Disease

Kanda

Suzuki²,

Toyama³

et al. 1995

Cardiology

View full text Add to dashboard Cite

The clinical implications of single-photon emission computed tomography using both a beta-methyl-branched fatty acid analog, ¹²³I-15-(ρ-idophenyl)-3-methyl-pentadecanoic acid (BMIPP), and thallium-201 (²⁰¹Tl) were assessed in 30 patients with myocardial infarction (MI), 8 diabetics, 4 patients with impaired glucose tolerance, and 18 nondiabetic patients. Discordant decreases in BMIPP uptake, as compared with ²⁰¹Tl uptake, in diabetic patients were significantly (p < 0.01) more frequent than in nondiabetic patients. The left ventricular (LV) ejection fraction in diabetics was significantly (p < 0.05) reduced and the LV diastolic dimension was significantly increased (p < 0.01), as compared with those in nondiabetic subjects. Analysis of peripheral blood showed no significant differences among the three test groups in metabolic abnormality. A discordant decrease in BMIPP uptake, as compared with Tl uptake, in cardiac tomography may indicate a metabolic derangement of the myocardium in diabetic patients with MI.

show abstract

Correlation of contractile dysfunction and abnormal tissue energy metabolism during hypoperfusion with norepinephrine in isolated rat hearts: Differences between normal and diabetic hearts

Cited by 9 publications

References 27 publications

Hyperglycemia can delay left ventricular dysfunction but not autonomic damage after myocardial infarction in rodents

Hyperglycemia can delay left ventricular dysfunction but not autonomic damage after myocardial infarction in rodents

Glycoxidative Stress and Cardiovascular Complications in Experimentally-Induced Diabetes: Effects of Antioxidant Treatment

Myocardial Uptake of an lodinated Branched Fatty Acid Analog, Assessed by SPECT, May Detect Metabolic Derangement of the Myocardium in Diabetic Patients with Coronary Heart Disease

Contact Info

Product

Resources

About