Development and feasibility of quantitative dynamic cardiac imaging for mice using µSPECT.

BACKGROUND: Despite growing interest in coronary microvascular disease (CMVD), there is a dearth of mechanistic understanding. Mouse models offer opportunities to understand molecular processes in CMVD. We have sought to develop quantitative mouse imaging to assess coronary microvascular function. METHODS: We used 99mTc-sestamibi to measure myocardial blood flow in mice with MILabs U-SPECT+ system. We determined recovery and crosstalk coefficients, the influx rate constant from blood to myocardium (K1), and, using microsphere perfusion, constraints on the extraction fraction curve. We used 99mTc and stannous pyrophosphate for red blood cell imaging to measure intramyocardial blood volume (IMBV) as an alternate measure of microvascular function. RESULTS: The recovery coefficients for myocardial tissue (RT) and left ventricular arterial blood (RA) were 0.81 ± 0.16 and 1.07 ± 0.12, respectively. The assumption RT = 1 - FBV (fraction blood volume) does not hold in mice. Using a complete mixing matrix to fit a one-compartment model, we measured K1 of 0.57 ± 0.08 min-1. Constraints on the extraction fraction curve for 99mTc-sestamibi in mice for best-fit Renkin-Crone parameters were α = 0.99 and ß = 0.39. Additionally, we found that wild-type mice increase their IMBV by 22.9 ± 3.3% under hyperemic conditions. CONCLUSIONS: We have developed a framework for measuring K1 and change in IMBV in mice, demonstrating non-invasive µSPECT-based quantitative imaging of mouse microvascular function.

[Cerebral effects of ketanserin. The influence on hemodynamics and brain metabolism]. / Zerebrale Effekte von Ketanserin. Der Einfluss auf die Hämodynamik und den Hirnstoffwechsel.

Ketanserin, a 5HT2- and alpha 1-receptor antagonist, decreases blood pressure by decreasing systemic vascular resistance without causing reflex cardiac stimulation, while cardiac output remains unchanged. To date, little is known about the effects of ketanserin on cerebral haemodynamics and cerebral metabolism. According to a recently published study, ketanserin seems not to impair cerebral blood flow autoregulation in man. The present study was designed to investigate the influence of ketanserin on cerebral circulation and metabolism, and the cerebrovascular response to CO2 in man. METHODS. Twenty male patients between 44 and 67 years of age who were scheduled for coronary artery bypass surgery were randomly allocated to one of two groups. In group 1 measurements were performed after induction of anaesthesia during normocapnia (p(a) CO2 approximately 40 mm Hg) and hypocapnia (p(a) CO2 approximately 30 mm Hg). Then, ketanserin was given at a bolus dose of 0.3 mg.kg-1 followed by an infusion of 0.06 mg.kg-1.h-1 and measurements were repeated under hypocapnic and normocapnic conditions. Patients of group 2 were hyperventilated at first, then normoventilated. Afterwards, ketanserin was administered at the above-mentioned dose and measurements were again performed during normocapnia and hypocapnia. Cerebral blood flow (CBF) was measured using the argon wash-in technique. Cerebral venous blood was obtained from a catheter in the superior bulb of the right internal jugular vein. Cerebral perfusion pressure (CPP) was calculated by subtracting jugular bulb pressure from mean arterial pressure and cerebral vascular resistance (CVR) by dividing CPP by CBF. Cerebral metabolic rates of oxygen, glucose, and lactate were calculated by multiplying the arterial-cerebral venous oxygen and substrate differences by CBF. RESULTS AND DISCUSSION. Ketanserin decreased CPP by 16% to about 60 mm Hg. Cerebral blood flow remained unchanged as a result of an insignificant decline in CVR. Hyperventilation increased CVR by 32%, while CBF decreased by 27% to the same value that had been obtained during hypocapnia without ketanserin. The percentage changes in CBF per mm Hg change in CO2 were 1.45%/mm Hg (group 1 and 2.91%/mm Hg (group 2), respectively, without ketanserin and 1.98%/mm Hg and 2.22%/mm Hg with ketanserin. As CO2-responsiveness with ketanserin was higher in group 1 but lower in group 2 than without ketanserin, the direction in which ventilation was changed rather than ketanserin was responsible for these changes in CO2-responsiveness. Neither during normocapnia nor during hypocapnia did ketanserin have any effects on cerebral metabolic activity. Thus, it can be concluded that ketanserin does not impair CBF regulation and metabolism and that cerebral vascular responsiveness to hypocapnia is preserved.