Neural Mechanisms of Tyrosine Kinase Inhibitor-Induced Hypertension in Humans
We will measure sympathetic nerve activity (SNA) with direct intraneural recording of sympathetic action potential (microneurography), skeletal muscle oxygenation (Noninvasive near Infrared spectroscopy), BP, forearm blood flow (high-resolution ultrasonography), forearm vascular resistance (FVR, the ratio of mean arterial pressure to forearm blood flow), cardiac output (noninvasive impedance plethysmography), total peripheral resistance (TPR, the ratio of mean arterial pressure to cardiac output) in 15 patients with hepatocellular carcinoma or renal cell carcinoma undergoing treatment with VEGF receptor (VEGFR) tyrosine kinase inhibitors such as sorafenib, sunitinib, or pazopanib, at baseline, during lower body negative pressure (LBNP) application alone to trigger reflex sympathetic activation alone, during handgrip exercise alone, and during both LBNP plus handgrip exercise. Then, we will repeat studies 4 weeks after VEGFR TKI treatment. We will also study another 15 patients with hepatocellular carcinoma or renal cell carcinoma undergoing other modalities of treatment such as chemoembolization without VEGFR TKIs separated by 4 weeks as the control group. Since sunitinib is approved by the FDA to be administered for 4 weeks followed 2 week period of drug washout, we will also repeat studies in subjects treated with sunitinib during period of drug washout for 2 weeks. The subjects will be recruited from the hepatocellular clinic and renal cell carcinoma clinic at the Simmons cancer center and Parkland Memorial hospital.
Both normotensive and hypertensive subjects with the age of ≥ 18 years can participate in the study provided blood pressure <140/90 mmHg before initiation of TKIs.
Inclusion Criteria for hepatocellular carcinoma: Patients must have a diagnosis of hepatocellular carcinoma, which is deemed to be unresectable or not eligible for hepatic transplantation. Determination will occur in the weekly meeting by surgical oncologists and transplant surgeons,
Inclusion Criteria for renal cell carcinoma: Patients must have at least one measurable metastatic site according to RECIST criteria (≥1 cm by spiral CT scan or ≥2 cm by conventional CT scan) that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.