Long chain n-3 polyunsaturated fatty acids and vascular function in patients with chronic kidney disease and healthy subjects:a cross-sectional and comparative study

BACKGROUND: Patients with chronic kidney disease have a markedly increased cardiovascular mortality compared with the general population. Long chain n-3 polyunsaturated fatty acids have been suggested to possess cardioprotective properties. This cross-sectional and comparative study evaluated correlations between hemodynamic measurements, resistance artery function and fish consumption to the content of long chain n-3 polyunsaturated fatty acids in adipose tissue, a long-term marker of seafood intake. METHODS: Seventeen patients with chronic kidney disease stage 5 + 5d and 27 healthy kidney donors were evaluated with hemodynamic measurements before surgery; from these subjects, 11 patients and 11 healthy subjects had vasodilator properties of subcutaneous resistance arteries examined. The measurements were correlated to adipose tissue n-3 polyunsaturated fatty acids. Information on fish intake was obtained from a dietary questionnaire and compared with adipose tissue n-3 polyunsaturated fatty acids. RESULTS: Fish intake and the content of n-3 polyunsaturated fatty acids in adipose tissue did not differ between patients and controls. n-3 polyunsaturated fatty acid levels in adipose tissue were positively correlated to systemic vascular resistance index; (r = 0.44; p = 0.07 and r = 0.62; p < 0.05, chronic kidney disease and healthy subjects respectively) and negatively correlated to cardiac output index (r = −0.69; p < 0.01 and r = −0.50; p < 0.05, chronic kidney disease and healthy subjects respectively). No correlation was observed between n-3 polyunsaturated fatty acid levels in adipose tissue and vasodilator properties in resistance arteries. n-3 PUFA content in adipose tissue increased with increasing self-reported fish intake. CONCLUSIONS: The correlations found, suggest a role for n-3 polyunsaturated fatty acids in hemodynamic properties. However, this is apparently not due to changes in intrinsic properties of the resistance arteries as no correlation was found to n-3 polyunsaturated fatty acids

Did giraffe cardiovascular evolution solve the problem of heart failure with preserved ejection fraction?

The evolved adaptations of other species can be a source of insight for novel biomedical innovation. Limitations of traditional animal models for the study of some pathologies are fueling efforts to find new approaches to biomedical investigation. One emerging approach recognizes the evolved adaptations in other species as possible solutions to human pathology. The giraffe heart, for example, appears resistant to pathology related to heart failure with preserved ejection fraction (HFpEF)-a leading form of hypertension-associated cardiovascular disease in humans. Here, we postulate that the physiological pressure-induced left ventricular thickening in giraffes does not result in the pathological cardiovascular changes observed in humans with hypertension. The mechanisms underlying this cardiovascular adaptation to high blood pressure in the giraffe may be a bioinspired roadmap for preventive and therapeutic strategies for human HFpEF

The thick left ventricular wall of the giraffe heart normalises wall tension, but limits stroke volume and cardiac output

Giraffes – the tallest extant animals on Earth – are renowned for their high central arterial blood pressure, which is necessary to secure brain perfusion. The pressure which may exceed 300 mmHg has historically been attributed to an exceptionally large heart. Recently, this has been refuted by several studies demonstrating that the mass of giraffe heart is similar to that of other mammals when expressed relative to body mass. It remains enigmatic, however, how the normal-sized giraffe heart generates such massive arterial pressures. We hypothesized that giraffe hearts have a small intraventricular cavity and a relatively thick ventricular wall, allowing for generation of high arterial pressures at normal left ventricular wall tension. In nine anaesthetized giraffes (495±38 kg), we determined in vivo ventricular dimensions using echocardiography along with intraventricular and aortic pressures to calculate left ventricular wall stress. Cardiac output was also determined by inert gas rebreathing to provide an additional and independent estimate of stroke volume. Echocardiography and inert gas-rebreathing yielded similar cardiac outputs of 16.1±2.5 and 16.4±1.4 l min−1, respectively. End-diastolic and end-systolic volumes were 521±61 ml and 228±42 ml, yielding an ejection fraction of 56±4%, and a stroke volume of 0.59 ml kg−1. Left ventricular circumferential wall stress was 7.83±1.76 kPa. We conclude that, relative to body mass, a small left ventricular cavity and a low stroke volume characterizes the giraffe heart. The adaptations result in typical mammalian left ventricular wall tensions, but results in lowered cardiac output.</jats:p

The regulation of pH in resistance arteries from spontaneously hypertensive and wistar-Kyoto rats: the effect of bicarbonate

Objective: To assess intracellular pH regulation in the presence of bicarbonate in resistance arteries from spontaneously hypertensive rats and Wistar-Kyoto (WKY) rats. Methods: Intracellular pH was determined in isolated resistance arteries from male adult SHR and WKY rats with the pH-sensitive fluorescent dye bis-carboxyethyl carboxyfluorescein, while the arteries were mounted in a myograph for simultaneous measurements of force. The arteries were acid-loaded using the ammonium chloride technique and the recovery from the acidosis was determined in resting arteries and in arteries activated with 50mmol/l potassium or arginine vasopressin. This protocol was performed in the presence and in the absence of bicarbonate. Results: In the absence of bicarbonate the intracellular pH was higher in resting arteries from SHR than in those from WKY rats, whereas during activation no significant difference was found. In the presence of bicarbonate no difference in intracellular pH between arteries from SHR and WKY rats could be found. The addition and washout of 15mmol/l ammonium chloride were associated with large force transients in activated arteries both from SHR and from WKY rats. The proton recovery rate at intracellular pH 6.85 in the absence of bicarbonate was higher in activated arteries from SHR than in those from WKY rats, whereas in resting arteries no significant difference was found. In the presence of bicarbonate no significant difference between SHR and WKY rat arteries was found. Conclusion: In the presence of bicarbonate a possible abnormality of the sodium-hydrogen exchange in resistance arteries from SHR is not manifested, because regulation of intracellular pH by bicarbonate-dependent mechanisms can compensate for such an abnormality