Low‐dose nitroglycerin improves microcirculation in hospitalized patients with acute heart failure

Abstract

AimsImpaired tissue perfusion is often observed in patients with acute heart failure. We tested whether low-dose nitroglycerin (NTG) improves microcirculatory perfusion in patients admitted for acute heart failure. Methods and resultsIn 20 acute heart failure patients, NTG was given as intravenous infusion at a fixed dose of 33 mg/min. Using Sidestream Dark Field (SDF) imaging, sublingual microvascular perfusion was evaluated before (T0, average of two baseline measurements) and 15 min after initiation of NTG (T1). In a subgroup of seven patients, SDF measurements were repeated after NTG had been stopped for 20 min. Capillaries were defined as microvessels with a diameter of ,20 mm. Perfused capillary density (PCD) was determined as the parameter of tissue perfusion. Values are expressed as median and interquartile range (P25; P75). The median age of the subjects was 60 (52; 73) years, and 65% were male. Patients were stable before starting NTG. Nitroglycerin decreased central venous pressure [17 (13; 19) mmHg at T0 vs. 16 (13; 17) mmHg at T1, P ¼ 0.03] and pulmonary capillary wedge pressure [23 (18; 31) mmHg at T0 vs. 19 (16; 25) mmHg at T1, P ¼ 0.03]. It increased PCD [10.7 (9.9; 12.5) mm mm 22 at T0 vs. 12.4 (11.4; 13.6) mm mm 22 at T1, P ¼ 0.01]. After cessation of NTG, PCD returned to baseline values (P ¼ 0.04). ConclusionLow-dose NTG significantly reduces cardiac filling pressures and improves microvascular perfusion in patients admitted for acute heart failure.--

Myocardial Microcirculation and Mitochondrial Energetics in the Isolated Rat Heart

“…The method is based on the oxygen dependent decay of delayed fluorescence of endogenously present mitochondrial protoporphyrin IX (P p IX) [24]. Proof of concept measurements were initially performed by Mik et al in single cells and later validated in vivo in rat liver and recently also in the heart [24,25]. Deconvolution of the decay curves allowed mit pO 2 histograms to be generated and showed a heterogeneous distribution of mit pO 2 values.…”

“…One of the remarkable measurements of the mit pO 2 values was the finding of mit pO 2 values much higher (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) than previously thought (less than 5 mmHg) and secondly the finding of markedly heterogeneous mit pO 2 values, similar to the distributions of microvascular pO 2 measurements using P p IX quenching of phosphorescence we had measured in heart [24]. Indeed (early) observations of the heterogeneous state of myocardial and mitochondrial energy states underscores the importance of heterogeneity of oxygen delivery and utilization [3].…”

Microcirculatory assessment in daily clinical practice - not yet ready but not too far!

“…Furthermore, vasodilators could also act on microcirculation reducing shunt areas and improving organ perfusion. Recently, den Uil et al demonstrated that nitroglycerin, a known vasodilator with NO donor properties, was able to reverse microcirculatory abnormalities in patients with acute heart failure (37) . However, whether correcting microcirculatory dysfunction will be associated with the improvement of patient outcome in a microcirculation-guided approach still remains to be proved.…”

“…However, no effect could be seen in endothelial histological injury or tissue factor expression in this same model. Nitroglycerin effects on microcirculation derangements had been tested in heart failure (37) and sepsis (60) . In acute heart failure, low doses of nitroglycerin (33 µg/min) increased perfused capillary density (assessed by SDF) for about 15% (37) .…”

“…Nitroglycerin effects on microcirculation derangements had been tested in heart failure (37) and sepsis (60) . In acute heart failure, low doses of nitroglycerin (33 µg/min) increased perfused capillary density (assessed by SDF) for about 15% (37) . Verapamil was shown to induce significant arteriolar dilatation, increase microvascular flow and functional capillary density, and decrease arteriolar transmural PO 2 difference of the awake hamster window chamber preparation (61) .…”