Low Mean Perfusion Pressure Indexed to Body Surface Area is a Powerful Predictor of Poor Outcomes After Heart Transplantation in Patients With High Pre-Transplant Venous Pressure: A Clinical Study With Physiological Insights From Mathematical Modelling of Biventricular Heart Failure.

BACKGROUND & AIM: The deleterious consequences of chronically elevated venous pressure in patients with profound right ventricular or biventricular dysfunction are well known, including renal and hepatic dysfunction, and volume overload. The only option for these patients, if they fail optimal medical treatment, is a heart transplant, as they are not candidates for left ventricular assist device therapy. Mean perfusion pressure (MPP) is important in the outcomes of critically ill patients with high venous pressure. The question arises whether MPP is important for the outcomes of heart transplants in patients with elevated pre-transplant venous pressure. Medical management of heart failure patients with reduced ejection fraction involves lowering the systemic afterload with vasodilators while awaiting a transplant. We hypothesised that when venous pressure is elevated prior to transplant, a substantial reduction in systemic arterial elastance (Ea) through vasodilation may significantly decrease MPP, resulting in compromised end-organ function and consequent unfavourable outcomes after heart transplantation. This study aims to investigate whether a low MPP serves as a risk factor for adverse outcomes in heart transplant recipients with high venous pressure. METHOD: A retrospective analysis was conducted on 250 heart transplant recipients undergoing isolated heart transplantation at a single institution from October 2012 to March 2020. Right atrial pressure (RAP) of more than 15 mmHg was considered high. Additionally, Ea calculated as the ratio of end-systolic pressure to stroke volume, and MPP calculated as the difference between mean arterial pressure and RAP were considered in our analysis. The outcomes of transplantation were measured in terms of 90-day mortality and survival up to 7 years. RESULTS: High RAP was a significant risk factor for short-term and medium-term survival if Ea was low (<2.7 mmHg/mL, the median value). This group had 39.39% in-hospital mortality compared to 14.49% for RAP<15 mmHg (p∼0.005). When Ea was high, this difference in survival was not evident: 8% for RAP<15 mmHg vs 4.8% for RAP>15 mmHg (p∼0.550). This effect was mediated through a lower MPP, and the mortality due to lower MPP increased strikingly with higher body surface area (BSA). A negative correlation was observed between MPP indexed to BSA (MPPI) and the Model for End-Stage Liver Disease score (r∼-0.3580, p<0.0001) as well as creatinine (r∼-0.3551, p<0.0001). MPPI less than 40 mmHg/m2 was associated with poorer short-term (23.2% for MPPI<40 mmHg/m2 vs 7.1% for MPPI>40 mmHg/m2, p∼0.001) and medium-term survival. The impact of high RAP and low Ea on survival was evident even on medium-term follow-up; only 30% survival at 7 years follow-up for high RAP and low Ea vs 75% for RAP<15 mmHg (p∼0.0033). CONCLUSION: The acceptable blood pressure during vasodilator therapy in patients with high RAP needs to be higher, especially in those with higher BSA. MPPI less than 40 mmHg/m2 is a risk factor for survival, in the short and medium-term, after heart transplantation.

4-(4-Chloro-phen-yl)-5-phenyl-isoxazole.

The title compound, C(15)H(10)ClNO, is a functionalized isoxazole with a chloro-phenyl and a phenyl substitutent. The mean plane of the isoxazole ring is inclined to those of the two benzene ring mean planes by 38.32 (16) and 43.91 (18)°.

2-(2,6-Dimethoxy-phen-yl)-5-hydr-oxy-7-meth-oxy-4H-1-benzopyran-4-one.

In the title compound, C(18)H(16)O(6), the dimethoxy-phenyl ring is rotated by 61.8 (1)° from the plane of the benzopyran system. The mol-ecule is stabilized by an intra-molecular O-H⋯O hydrogen bond.

(E)-3-[2-(4-Chloro-phenyl-sulfon-yl)vin-yl]-6-methyl-4H-chromen-4-one.

In the title compound, C(18)H(13)ClO(4)S, the mean planes of the chloro-phenyl ring and the S-C=C-C chain are oriented at angles of 52.7 (2) and 51.3 (2)°, respectively, with respect to the sulfonyl (O=S=O) plane. The dihedral angle between the mean planes of the chloro-phenyl group and the benzopyran ring is 80.7 (1)°. The crystal structure is stabilized by two inter-molecular C-H⋯O inter-actions, forming centrosymmetrc dimers, which are linked via a second C-H⋯O inter-action into a chain structure.

2-Bromo-1,2-diphenylethenyl 4-methyl-phenyl sulfoxide.

In the title compound, C(21)H(17)BrO(2)S, the two phenyl rings attached to the ethene group are oriented at dihedral angles of 76.19 (10) and 57.99 (8)° with respect to the Br-C=C-S plane [r.m.s. deviation 0.003 Å]. The sulfonyl-bound phenyl ring forms a dihedral angle of 83.26 (8)° with the above plane. The crystal structure is stabilized by weak C-H⋯π inter-actions.

Present susceptibility status of rat flea Xenopsylla cheopis (Siphonaptera: Pulicidae), vector of plague against organochlorine, organophosphate and synthetic pyrethroids 1. The Nilgiris District, Tamil Nadu, India.

The susceptibility status of Xenopsylla cheopis, the efficient vector of human plague in India was assessed in erstwhile plague endemic areas of Nilgiris district, Tamil Nadu following standard WHO techniques. The studies revealed the development of resistance in rat fleas to DDT--4.0%, Malathion--5.0%, Deltamethrin--0.05% and tolerance to Permethrin--0.75% in all the four blocks of Nilgiris hill district. Development of resistance may be due to the extensive use of insecticides in tea plantations and agricultural sectors where the domestic/peri-domestic rodents find their natural habitats and intermingle with each other.